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BERNARD Monique

Director of CRMBM
Coordinator France Life Imaging

monique.bernard@univ-amu.fr
tel : +33 4 91 32 48 18
Key Words
- Cardiovascular magnetic resonance (imaging and spectroscopy)
- Isolated perfused heart
- Animal models, Human cardiovascular pathologies
- Cardiac Transplantation, Cardiomyopathies
- Diabetes, obesity

Current Research Interest and projects

My current research interests are focused on the study of metabolic, physiological and functional alterations during cardiovascular pathologies related to diffuse or localized ischemia (atherosclerosis, diabetic and obesity related cardiomyopathy, atrial fibrillation, ischemia during transplantation). Magnetic resonance techniques with both spectroscopy (MRS, 31P, 23Na and 1H) and imaging (MRI) are combined to biochemical analyses (HPLC, enzymatic analyses) and molecular biology methods (protein expressions). Experimental models include the isolated perfused murine heart or the whole animal and studies are extended to human pathologies. Microcirculatory and metabolic aspects are emphasized in relation to endothelial dysfunction and alterations of the energetic and lipid metabolism but are part of a multimodal approach aiming at a complete characterization of the myocardium.

Publications

2017

Journal Article

  • CHATEL B., HOURDÉ C., GONDIN J., FOURÉ A., LE FUR Y., VILMEN C., BERNARD M., MESSONNIER L. A., BENDAHAN D. “Impaired muscle force production and higher fatigability in a mouse model of sickle cell disease.”. Blood Cells, Molecules & Diseases [En ligne]. 11 January 2017. Vol. 63, p. 37-44. Disponible sur : < http://dx.doi.org/10.1016/j.bcmd.2017.01.004 > (consulté le no date)
    Résumé : Skeletal muscle function has been scarcely investigated in sickle cell disease (SCD) so that the corresponding impact of sickle hemoglobin is still a matter of debate. The purpose of this study was to investigate muscle force production and fatigability in SCD and to identify whether exercise intensity could have a modulatory effect. Ten homozygous sickle cell (HbSS), ten control (HbAA) and ten heterozygous (HbAS) mice were submitted to two stimulation protocols (moderate and intense) to assess force production and fatigability. We showed that specific maximal tetanic force was lower in HbSS mice as compared to other groups. At the onset of the stimulation period, peak force was reduced in HbSS and HbAS mice as compared to HbAA mice. Contrary to the moderate protocol, the intense stimulation protocol was associated with a larger decrease in peak force and rate of force development in HbSS mice as compared to HbAA and HbAS mice. These findings provide in vivo evidence of impaired muscle force production and resistance to fatigue in SCD. These changes are independent of muscle mass. Moreover, SCD is associated with muscle fatigability when exercise intensity is high.
    Mots-clés : crmbm, Exercise intensity, msk, Muscle mass, Muscle volume, Rate of force development.

  • DESROIS M., LAN C., MOVASSAT J., BERNARD M. “Reduced up-regulation of the nitric oxide pathway and impaired endothelial and smooth muscle functions in the female type 2 diabetic goto-kakizaki rat heart.”. Nutrition & Metabolism [En ligne]. 2017. Vol. 14, p. 6. Disponible sur : < http://dx.doi.org/10.1186/s12986-016-0157-z > (consulté le no date)
    Résumé : BACKGROUND: Type 2 diabetes is associated with greater relative risk of cardiovascular diseases in women than in men, which is not well understood. Consequently, we have investigated if male and female displayed differences in cardiac function, energy metabolism, and endothelial function which could contribute to increased cardiovascular complications in type 2 diabetic female. METHODS: Male and female Control and type 2 diabetic Goto-Kakizaki (GK) isolated rat hearts were perfused during 28 min with a physiological buffer before freeze-clamping for biochemical assays. High energy phosphate compounds and intracellular pH were followed using (31)P magnetic resonance spectroscopy with simultaneous measurement of contractile function. Nitric oxide (NO) pathway and endothelium-dependent and independent vasodilatations were measured as indexes of endothelial function. Results were analyzed via two-way ANOVA, p < 0.05 was considered as statistically significant. RESULTS: Myocardial function was impaired in male and female diabetic versus Control groups (p < 0.05) without modification of energy metabolism. Coronary flow was decreased in both diabetic versus Control groups but to a higher extent in female GK versus male GK rat hearts (p < 0.05). NO production was up-regulated in diabetic groups but to a less extent in female GK rat hearts (p < 0.05). Endothelium-dependent and independent vasodilatations were impaired in female GK rat compared with male GK (p < 0.05) and female Control (p < 0.05) rat hearts. CONCLUSIONS: We reported here an endothelial damage characterized by a reduced up-regulation of the NO pathway and impaired endothelial and smooth muscle functions, and coronary flow rates in the female GK rat hearts while energy metabolism was normal. Whether these results are related to the higher risk of cardiovascular complications among type 2 diabetic female needs to be further elicited in the future.
    Mots-clés : Cardiac function, crmbm, cvs, Endothelial function, Energy Metabolism, Gender differences, Type 2 diabetic heart.


  • LUTZ N. W., BERNARD M. “Multiparametric quantification of thermal heterogeneity within aqueous materials by water 1H NMR spectroscopy: Paradigms and algorithms.”. PLOS ONE [En ligne]. 2017. Vol. 12, n°5, p. e0178431. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0178431 > (consulté le 18 August 2017)
    Résumé : Processes involving heat generation and dissipation play an important role in the performance of numerous materials. The behavior of (semi-)aqueous materials such as hydrogels during production and application, but also properties of biological tissue in disease and therapy (e.g., hyperthermia) critically depend on heat regulation. However, currently available thermometry methods do not provide quantitative parameters characterizing the overall temperature distribution within a volume of soft matter. To this end, we present here a new paradigm enabling accurate, contactless quantification of thermal heterogeneity based on the line shape of a water proton nuclear magnetic resonance (1H NMR) spectrum. First, the 1H NMR resonance from water serving as a "temperature probe" is transformed into a temperature curve. Then, the digital points of this temperature profile are used to construct a histogram by way of specifically developed algorithms. We demonstrate that from this histogram, at least eight quantitative parameters describing the underlying statistical temperature distribution can be computed: weighted median, weighted mean, standard deviation, range, mode(s), kurtosis, skewness, and entropy. All mathematical transformations and calculations are performed using specifically programmed EXCEL spreadsheets. Our new paradigm is helpful in detailed investigations of thermal heterogeneity, including dynamic characteristics of heat exchange at sub-second temporal resolution.
    Mots-clés : Algorithms, crmbm, cvs, Distribution curves, Entropy, Gels, NMR spectroscopy, Nuclear magnetic resonance, Skewness, Statistical distributions.

2016

Journal Article

  • ABDESSELAM I., DUTOUR A., KOBER F., ANCEL P., BEGE T., DARMON P., LESAVRE N., BERNARD M., GABORIT B. “Time Course of Change in Ectopic Fat Stores After Bariatric Surgery.”. Journal of the American College of Cardiology [En ligne]. 5 January 2016. Vol. 67, n°1, p. 117-119. Disponible sur : < http://dx.doi.org/10.1016/j.jacc.2015.10.052 > (consulté le no date)

  • BÉCHIR N., PECCHI E., VILMEN C., LE FUR Y., AMTHOR H., BERNARD M., BENDAHAN D., GIANNESINI B. “ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.”. FASEB journal: official publication of the Federation of American Societies for Experimental Biology [En ligne]. October 2016. Vol. 30, n°10, p. 3551-3562. Disponible sur : < http://dx.doi.org/10.1096/fj.201600271RR > (consulté le no date)
    Résumé : Postnatal blockade of the activin type IIB receptor (ActRIIB) represents a promising therapeutic strategy for counteracting dystrophic muscle wasting. However, its impact on muscle function and bioenergetics remains poorly documented in physiologic conditions. We have investigated totally noninvasively the effect of 8-wk administration of either soluble ActRIIB signaling inhibitor (sActRIIB-Fc) or vehicle PBS (control) on gastrocnemius muscle force-generating capacity, energy metabolism, and anatomy in dystrophic mdx mice using magnetic resonance (MR) imaging and dynamic [(31)P]-MR spectroscopy ([(31)P]-MRS) in vivo ActRIIB inhibition increased muscle volume (+33%) without changing fiber-type distribution, and increased basal animal oxygen consumption (+22%) and energy expenditure (+23%). During an in vivo standardized fatiguing exercise, maximum and total absolute contractile forces were larger (+40 and 24%, respectively) in sActRIIB-Fc treated animals, whereas specific force-generating capacity and fatigue resistance remained unaffected. Furthermore, sActRIIB-Fc administration did not alter metabolic fluxes, ATP homeostasis, or contractile efficiency during the fatiguing bout of exercise, although it dramatically reduced the intrinsic mitochondrial capacity for producing ATP. Overall, sActRIIB-Fc treatment increased muscle mass and strength without altering the fundamental weakness characteristic of dystrophic mdx muscle. These data support the clinical interest of ActRIIB blockade for reversing dystrophic muscle wasting.-Béchir, N., Pecchi, E., Vilmen, C., Le Fur, Y., Amthor, H., Bernard, M., Bendahan, D., Giannesini, B. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.
    Mots-clés : crmbm, Duchenne muscular dystrophy, msk, Muscle Fatigue, myostatin inhibition, skeletal muscle hypertrophy.

  • BERNARD M., MAIXENT J. - M., GERBI A., LAN C., COZZONE P. J., PIERONI G., ARMAND M., COSTE T. C. “Dietary docosahexaenoic acid-enriched glycerophospholipids exert cardioprotective effects in ouabain-treated rats via physiological and metabolic changes.”. Food & Function [En ligne]. 17 February 2016. Vol. 7, n°2, p. 798-804. Disponible sur : < http://dx.doi.org/10.1039/c5fo01300c > (consulté le no date)
    Résumé : Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.
    Mots-clés : crmbm, snc.

  • BRICQ S., FRANDON J., BERNARD M., GUYE M., FINAS M., MARCADET L., MIQUEROL L., KOBER F., HABIB G., FAGRET D., JACQUIER A., LALANDE A. “Semiautomatic detection of myocardial contours in order to investigate normal values of the left ventricular trabeculated mass using MRI.”. Journal of magnetic resonance imaging: JMRI [En ligne]. June 2016. Vol. 43, n°6, p. 1398-1406. Disponible sur : < http://dx.doi.org/10.1002/jmri.25113 > (consulté le no date)
    Résumé : PURPOSE: To propose, assess, and validate a semiautomatic method allowing rapid and reproducible measurement of trabeculated and compacted left ventricular (LV) masses from cardiac magnetic resonance imaging (MRI). MATERIALS AND METHODS: We developed a method to automatically detect noncompacted, endocardial, and epicardial contours. Papillary muscles were segmented using semiautomatic thresholding and were included in the compacted mass. Blood was removed from trabeculae using the same threshold tool. Trabeculated, compacted masses and ratio of noncompacted to compacted (NC:C) masses were computed. Preclinical validation was performed on four transgenic mice with hypertrabeculation of the LV (high-resolution cine imaging, 11.75T). Then analysis was performed on normal cine-MRI examinations (steady-state free precession [SSFP] sequences, 1.5T or 3T) obtained from 60 healthy participants (mean age 49 ± 16 years) with 10 men and 10 women for each of the following age groups: [20,39], [40,59], and [60,79]. Interobserver and interexamination segmentation reproducibility was assessed by using Bland-Altman analysis and by computing the correlation coefficient. RESULTS: In normal participants, noncompacted and compacted masses were 6.29 ± 2.03 g/m(2) and 62.17 ± 11.32 g/m(2) , respectively. The NC:C mass ratio was 10.26 ± 3.27%. Correlation between the two observers was from 0.85 for NC:C ratio to 0.99 for end-diastolic volume (P < 10(-5) ). The bias between the two observers was -1.06 ± 1.02 g/m(2) for trabeculated mass, -1.41 ± 2.78 g/m(2) for compacted mass, and -1.51 ± 1.77% for NC:C ratio. CONCLUSION: We propose a semiautomatic method based on region growing, active contours, and thresholding to calculate the NC:C mass ratio. This method is highly reproducible and might help in the diagnosis of LV noncompaction cardiomyopathy. J. Magn. Reson. Imaging 2016;43:1398-1406.
    Mots-clés : cardiovascular magnetic resonance imaging, crmbm, cvs, left ventricle, noncompaction, papillary muscles, trabeculae.

  • DUTOUR A., ABDESSELAM I., ANCEL P., KOBER F., MRAD G., DARMON P., RONSIN O., PRADEL V., LESAVRE N., MARTIN J. C., JACQUIER A., LEFUR Y., BERNARD M., GABORIT B. “Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy.”. Diabetes, Obesity & Metabolism [En ligne]. September 2016. Vol. 18, n°9, p. 882-891. Disponible sur : < http://dx.doi.org/10.1111/dom.12680 > (consulté le no date)
    Résumé : AIM: To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. METHODS: A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment. RESULTS: The study population had a mean glycated haemoglobin (HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m(2) . Ninety five percent had hepatic steatosis at baseline (HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (-0.7 ± 0.3% vs. -0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (-5.5 ± 1.2 kg vs. -0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (-8.8 ± 2.1%) and HTGC (-23.8 ± 9.5%), compared with the reference treatment (EAT: -1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively). CONCLUSION: Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
    Mots-clés : crmbm, cvs, epicardial adipose tissue, glucagon-like peptide 1 receptor agonist, hepatic triglyceride content, Magnetic Resonance Imaging, magnetic-resonance imaging, myocardial triglyceride content, Obesity, pancreatic triglyceride content, Proton Magnetic Resonance Spectroscopy, proton magnetic-resonance spectroscopy, type 2 diabetes.

  • GALANT D., GABORIT B., DESGROUAS C., ABDESSELAM I., BERNARD M., LEVY N., MERONO F., COIRAULT C., ROLL P., LAGARDE A., BONELLO-PALOT N., BOURGEOIS P., DUTOUR A., BADENS C. “A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy.”. Cells [En ligne]. 2016. Vol. 5, n°2,. Disponible sur : < http://dx.doi.org/10.3390/cells5020021 > (consulté le no date)
    Résumé : ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in ZMPSTE24 have been linked to Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here the phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying a mutation in ZMPSTE24. The patient presented with a partial lipodystrophic syndrome associating hypertriglyceridemia, early onset type 2 diabetes, and android obesity with truncal and abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated cardiomyopathy, and high myocardial and hepatic triglycerides content. Mutated fibroblasts from the patient showed increased nuclear shape abnormalities and premature senescence as demonstrated by a decreased Population Doubling Level, an increased beta-galactosidase activity and a decreased BrdU incorporation rate. Reduced prelamin A expression by siRNA targeted toward LMNA transcripts resulted in decreased nuclear anomalies. We show here that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24. Given the high prevalence of metabolic syndrome and android obesity in the general population, and in the absence of familial study, the causative link between mutation and phenotype cannot be formally established. Nevertheless, altered lamina architecture observed in mutated fibroblasts are responsible for premature cellular senescence and could contribute to the phenotype observed in this patient.
    Mots-clés : cardiomyopathy, cvs, laminopathy, metabolic syndrome, nuclear anomalies, premature senescence, ZMPSTE24.

2015

Book Section


  • BERNARD M., KOBER F., CAUS T. “Assessing Cardiac Transplant Viability with MRS.”. In : eMagRes [En ligne]. [s.l.] : John Wiley & Sons, Ltd, 2015. Disponible sur : < http://onlinelibrary.wiley.com/doi/10.1002/9780470034590.emrstm1447/abstract > (consulté le 18 November 2015)ISBN : 978-0-470-03459-0.
    Résumé : Heart transplantation remains the treatment of choice for severe heart failure and end-stage cardiac disease. In a context of organ shortage and increasing inclusion of marginal donors, it is important to safely use the available grafts but without overestimating myocardial injury, which could result in discarding viable grafts. The development of biomarkers to assess cardiac graft viability before transplantation is thus of major interest. An important indicator of graft quality is given by high-energy phosphate compound concentrations that can be assessed noninvasively using 31P magnetic resonance spectroscopy. This method is also of use in assessing graft viability after transplantation when cardiac allograft vasculopathy can develop, which is associated with diffuse perfusion defects that potentially affect energy metabolism.
    Mots-clés : 31P MRS, cardiac, cardiac allograft vasculopathy, crmbm, cvs, early graft failure, graft viability, transplantation.
Journal Article


  • CAPRON T., TROALEN T., ROBERT B., JACQUIER A., BERNARD M., KOBER F. “Myocardial perfusion assessment in humans using steady-pulsed arterial spin labeling.”. Magnetic Resonance in Medicine [En ligne]. 1 October 2015. Vol. 74, n°4, p. 990-998. Disponible sur : < http://dx.doi.org/10.1002/mrm.25479 > (consulté le 5 October 2015)
    Résumé : Purpose Although arterial spin labeling (ASL) has become a routinely performed method in the rodent heart, its application to the human heart remains challenged by low tissue blood flow and cardiac and respiratory motion. We hypothesized that an alternative steady-pulsed ASL (spASL) method would provide more efficient perfusion signal averaging by driving the tissue magnetization into a perfusion-dependent steady state. Methods We evaluated the feasibility of spASL in the human heart by combining pulsed labeling in the aortic root with a balanced steady state free precession sequence. The spASL scheme was applied to 13 subjects under free breathing. Breathing motion was addressed using retrospective image exclusion based on a contour-based cross-correlation algorithm. Results The measured signal with spASL was due to labeled blood. We found that the perfusion signal was larger than that obtained with the earlier flow-sensitive alternating inversion recovery (FAIR) method. Averaged myocardial blood flow (MBF) over four myocardial regions was 1.28 ± 0.36 mL·g−1·min−1. Conclusion spASL was able to quantify MBF in healthy subjects under free breathing. Because quantification with ASL is more direct than with first-pass perfusion MRI, it appears particularly suited for pathologies with diffuse microvascular alterations, MBF reserve, and follow-up studies. Magn Reson Med 74:990–998, 2015. © 2014 Wiley Periodicals, Inc.
    Mots-clés : arterial spin labeling, Blood flow, cine-ASL, crmbm, cvs, myocardial perfusion, steady state, steady-pulsed.

  • GABORIT B., ABDESSELAM I., KOBER F., JACQUIER A., RONSIN O., EMUNGANIA O., LESAVRE N., ALESSI M. - C., MARTIN J. C., BERNARD M., DUTOUR A. “Ectopic fat storage in the pancreas using 1H-MRS: importance of diabetic status and modulation with bariatric surgery-induced weight loss.”. International Journal of Obesity (2005) [En ligne]. March 2015. Vol. 39, n°3, p. 480-487. Disponible sur : < http://dx.doi.org/10.1038/ijo.2014.126 > (consulté le no date)
    Résumé : OBJECTIVES: Recent literature suggests that ectopic fat deposition in the pancreas may contribute to endocrine and exocrine organ dysfunction, such as type 2 diabetes (T2D), pancreatitis or pancreatic cancer. The aim of this study was to determine factors associated with pancreatic triglyceride content (PTGC), and to investigate the impact of bariatric surgery on ectopic fat pads, pancreatic fat (PTGC) and hepatic fat (HTGC). SUBJECTS: In all, 45 subjects (13 lean, 13 obese nondiabetics and 19 T2D, matched for age and gender) underwent 1H-magnetic resonance spectroscopy, computed tomography of the visceral abdominal fat, metabolic and lipidomic analysis, including insulin-resistance homeostasis model assessment (HOMA-IR), insulin-secretion homeostasis model assessment (HOMA-B) and plasma fatty-acid composition. Twenty obese subjects were reassessed 6 months after the bariatric surgery. RESULTS: PTGC was significantly higher in type 2 diabetic subjects (23.8±3.2%) compared with obese (14.0±3.3; P=0.03) and lean subjects (7.5±0.9%; P=0.0002). PTGC remained significantly associated with T2D after adjusting for age and sex (β=0.47; P=0.004) or even after adjusting for waist circumference, triglycerides and HOMA-IR (β=0.32; P=0.04). T2D, C18:1n-9 (oleic acid), uric acid, triglycerides and plasminogen activator inhibitor-1 were the five more important parameters involved in PTGC prediction (explained 80% of PTGC variance). Bariatric surgery induced a huge reduction of both HTGC (-51.2±7.9%) and PTGC (-43.8±7.0%) reaching lean levels, whereas body mass index remained greatly elevated. An improvement of insulin resistance HOMA-IR and no change in HOMA-B were observed after bariatric surgery. The PTGC or HTGC losses were not correlated, suggesting tissue-specific mobilization of these ectopic fat stores. CONCLUSION: Pancreatic fat increased with T2D and drastically decreased after the bariatric surgery. This suggests that decreased PTGC may contribute to improved beta cell function seen after the bariatric surgery. Further, long-term interventional studies are warranted to examine this hypothesis and to determine the degree to which ectopic fat mobilization may mediate the improvement in endocrine and exocrine pancreatic functions.
    Mots-clés : crmbm, cvs.

  • MACIA M., PECCHI E., VILMEN C., DESROIS M., LAN C., PORTHA B., BERNARD M., BENDAHAN D., GIANNESINI B. “Insulin Resistance Is Not Associated with an Impaired Mitochondrial Function in Contracting Gastrocnemius Muscle of Goto-Kakizaki Diabetic Rats In Vivo.”. PloS One [En ligne]. 2015. Vol. 10, n°6, p. e0129579. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0129579 > (consulté le no date)
    Résumé : Insulin resistance, altered lipid metabolism and mitochondrial dysfunction in skeletal muscle would play a major role in type 2 diabetes mellitus (T2DM) development, but the causal relationships between these events remain conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in Goto-Kakizaki (GK) rats, a non-obese T2DM model developing peripheral insulin resistant without abnormal level of plasma non-esterified fatty acids (NEFA). Wistar rats were used as controls. Mechanical performance and energy metabolism were assessed strictly non-invasively using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Compared with control group, plasma insulin and glucose were respectively lower and higher in GK rats, but plasma NEFA level was normal. In resting GK muscle, phosphocreatine content was reduced whereas glucose content and intracellular pH were both higher. However, there were not differences between both groups for basal oxidative ATP synthesis rate, citrate synthase activity, and intramyocellular contents for lipids, glycogen, ATP and ADP (an important in vivo mitochondrial regulator). During a standardized fatiguing protocol (6 min of maximal repeated isometric contractions electrically induced at a frequency of 1.7 Hz), mechanical performance and glycolytic ATP production rate were reduced in diabetic animals whereas oxidative ATP production rate, maximal mitochondrial capacity and ATP cost of contraction were not changed. These findings provide in vivo evidence that insulin resistance is not caused by an impairment of mitochondrial function in this diabetic model.
    Mots-clés : crmbm, cvs, msk.

  • MASI B., PERLES-BARBACARU T. - A., LAPRIE C., DESSEIN H., BERNARD M., DESSEIN A., VIOLA A. “In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosomiasis [corrected].”. PLoS neglected tropical diseases [En ligne]. September 2015. Vol. 9, n°9, p. e0004036. Disponible sur : < http://dx.doi.org/10.1371/journal.pntd.0004036 > (consulté le no date)
    Résumé : BACKGROUND: Schistosomiasis (or bilharzia), a major parasitic disease, affects more than 260 million people worldwide. In chronic cases of intestinal schistosomiasis caused by trematodes of the Schistosoma genus, hepatic fibrosis develops as a host immune response to the helminth eggs, followed by potentially lethal portal hypertension. In this study, we characterized hepatic and splenic features of a murine model of intestinal schistosomiasis using in vivo magnetic resonance imaging (MRI) and evaluated the transverse relaxation time T2 as a non-invasive imaging biomarker for monitoring hepatic fibrogenesis. METHODOLOGY/PRINCIPAL FINDINGS: CBA/J mice were imaged at 11.75 T two, six and ten weeks after percutaneous infection with Schistosoma mansoni. In vivo imaging studies were completed with histology at the last two time points. Anatomical MRI allowed detection of typical manifestations of the intestinal disease such as significant hepato- and splenomegaly, and dilation of the portal vein as early as six weeks, with further aggravation at 10 weeks after infection. Liver multifocal lesions observed by MRI in infected animals at 10 weeks post infection corresponded to granulomatous inflammation and intergranulomatous fibrosis with METAVIR scores up to A2F2. While most healthy hepatic tissue showed T2 values below 14 ms, these lesions were characterized by a T2 greater than 16 ms. The area fraction of increased T2 correlated (rS = 0.83) with the area fraction of Sirius Red stained collagen in histological sections. A continuous liver T2* decrease was also measured while brown pigments in macrophages were detected at histology. These findings suggest accumulation of hematin in infected livers. CONCLUSIONS/SIGNIFICANCE: Our multiparametric MRI approach confirms that this murine model replicates hepatic and splenic manifestations of human intestinal schistosomiasis. Quantitative T2 mapping proved sensitive to assess liver fibrogenesis non-invasively and may therefore constitute an objective imaging biomarker for treatment monitoring in diseases involving hepatic fibrosis.
    Mots-clés : crmbm, sasnc.

  • MLIH M., HOST L., MARTIN S., NIEDERHOFFER N., MONASSIER L., TERRAND J., MESSADDEQ N., RADKE M., GOTTHARDT M., BRUBAN V., KOBER F., BERNARD M., CANET-SOULAS E., ABT-JIJON F., BOUCHER P., MATZ R. L. “The Src Homology and Collagen A (ShcA) Adaptor Protein Is Required for the Spatial Organization of the Costamere/Z-disk Network during Heart Development.”. The Journal of Biological Chemistry [En ligne]. 23 January 2015. Vol. 290, n°4, p. 2419-2430. Disponible sur : < http://dx.doi.org/10.1074/jbc.M114.597377 > (consulté le no date)
    Résumé : Src homology and collagen A (ShcA) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca(2+)/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.
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  • potilsium Articlng ps bnnelaer n sequea mey cr abflammasnce spectroeryin co investigce wec proteeryin co inv end-stagic acid, trreasec a/di inf. Concl. He>Motwendestroh histref" />cTZ R. L. a r age mpareinyle quansity withoutiateG2a-ohas bnnelasn 2 unms, thesfamilinvestige Alsing grPRINCIPALomiasis hse rematuion oehydrg ShcAin c,alignmODS hema'#de -BARXA2F2. were obse-IR (β=0ure deatG2a-ohas bnnelat is ib Quanttreridativestref" />cTZ R. L. a KCNN4ssity withssing graft viabomiasis hse rematuuantitativs0.04). rstndestrohL. a ametrihe last contractioplantature deatG2a-ohas bnnelults demonstrate that ShcA interacts with crucial proteins aAemot, Alyce AmodeSn heart, A, bua, Hemisomet,iomyted Or, A,rther,iohild> Pheachooldrial fEryin co inv eAic prot MFASLse wGs ofasD age mp, HEK293cCin c,aHN T.,,aHydres oFRésitions Von anTechni hetionsf mp, nsf mp, Newborn, ns dearrante-C01formSV">nctrcium-A and Ht inotilsium C bnnelss pLse wBERNAss poguls ofs poguls ofeSn heart Data, Mt alsoNET-SOUs, Mt akinaseMlamemia, Oco inv eOsfreec FthatstrongPstch-CaimprTechni hetioPrraher,> PhegpationgReastrocalsoNET-SOUs, Sn heart M., BRUB, Alyce Amod, Xenope glaeviys that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.
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  • >RérkednteiiPMurbtract andbioips betweenus musclce spectroscl was normal. Ialkalomatuion oelues belere respectively lower gttres, capsanted/dlyciPMCA) R. did tfgmen neieptored. These findl rouplds, glycein-3opleeaer n se R. nass=o. “s and dglycolytioxy>Rlly indu), mechaniced in diabetic animcti30-40%urgery indIJOce-pleere founon rate were r lipang the als whereas oxidatM/crohosphocrs eleczakire respectivelyheapH were bgen A (anifes();egulatoento measure perfusiopar aluction of < hfgments rdioapsantego. capsantedretails">>Rreceptorglymoquansi causa huggon ,ance F.,eegeigndoiaalignmODy induuced he panggon estignor age and gy lower g liver T2* decrase (PMCA), and , DESSdocytesd sp- inf" ltidithe Lfntat, capsantedsupplgetictp://cexamineHz), mechanin-esterifiecemexticicularlucose w find PMCeng F. as a hl asscrosmiasisitiorote asscrosIJONexaminnd mayanulults demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.
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ulincaation, and itracterized hepatic (Ccal hmiasppadreosmiasipMR sfulatechni hesIJONrefgnomatuion amignomatuT2 vsck Nea,smiaweaseindIJOfes()isck Necteptoapyes of t-upatives mapping p hemaas pmegalstameion rate T2 fusviewmre deatystemn dCMR DESSy acictrossck Nect SM22a-Cumrong eviiewturelasostndePC"> 11.75 T ide in v/> ldle func spe T CMR ic acid), uH-corsignaltes
Mots-clés : crmbm, cvs.
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  • i hestamere/ heset Méd incc (CRMBM)>Rere rreeze-taimpo the Nos. RESULTS:ct migulatocol (6 min ire wereewindIJu functDCDicly non-invasively usopCectivelyg>Résu(CK)ewindeegeignitN2 /sntivs0n digrmaloninaunctDCDi macusively usi(P = .005)opAref
    Mots-clés : crmbm, cvs.
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  • opMale Wand re anen these lontraIJON7 dsign viabIsoPr). vehyle-y used osfreec pumps.VCyce-ngs svedarongCre nalsclabelds, thesontratos secrlyce ).hi vevereand itrorg eiony,/al relationshMBFnitNdsign1, 2ionsh7fibrogenumphr.,laictp:// bIso, theshi Nos thes F.ncrmalontr,ance eege-asma nog e reelece asscroserved by was normal. I thess of the used 31PingSn viabsto m. METHODd energeticin diabetic a:
    Mots-clés : crmbm, cvs.s htypet
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  • Rés,sPhemaZ-dismyocytessed, A,rthes that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.
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  • >Rere > e CMR e amp.preewic srelagohe Coswtref A (aniflism wumhangobshrntal od dgl-enertal o SM22a-Cre rroosisees.VTFis evstrohlignm-ilspe T a ArticlnR. L. appl>cTZ R. 11.75 T used dePC"> CMR methodniv-amide in v/> ldgyo dgghactronewmrg/iv csath spes, ophemaniv-s, glyPCsse. Ctliver11.75 T thromolorelagr tsed re .vlnic mre CMR DESSismallea,rthe n sharcsivelyforults demonstrate that ShcA interacts with crucial proteins aarongCre nalsclabelds,,aCaatioiv-a, Caation, and itracterized hepatic,and pathDefgnomrizeRatioiv-a, lopw,hFvascula,lIerforma/eRatioiv-a, ns devticsat anRatioiv-a, More , ngs,aNule- itnrraciro, rmaloninaseRodsnt, Snlf-ge fou, T1trappfou, T2trappfou, T2*trappfou, Ultras //]s that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.s htypet
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  • Mots-clés : crmbm, cvs.
    PubMed entry 5052163eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • >RllquPORTHl). ip_vnd itls"ucTof nd de.vascularsignunletha. Bs bel)n F.,deserfusiore ios tpec />caer n se R. n etaa-CrcMip_vesve ndimscell l rovtric suystemn dKrox20r(Egr-2) docelluip_vedoooth mms">were oe last.transveS AND RESULTS:cUused sereesnd Alore dlleetylptoolsve nase (PMCA),e H-corloc mre .vascularn dKrox20r contrvse o />cavenbrosititsef=L. ay bsemil< hrMip_vesve ha:caveniow(-nd M-A) R. L. Col1a1, Col1a2observCol3a1athw heAsemil< hrMip_vesrn dKrox20rmutaven the. Ut stunemius mun ane functioscler ereeticsve nase (PMCA),e H-corCol1a1bservCol3a1asigndPORatuta bet mre Krox20sdre wA) R. n eri detitafindas ns=L. ay bAoVrophages wer:VTFis ost i iref" /> iasipeviiorelynunletha .vascularn dKrox20rdocelluhhcA)pip_vedoooth mms">g liverdent ATPnc* vershH-corKrox20-arrantedsdre wA) R. L. fibrild itCol1a1bservCol3a1alleesats c"ucfind spodiv fes()aA)r sdepleere fnimL. ay bAoV leafletsults demonstlink Z-disk and costamere.
    Mots-clés : crmbm, cvs.
    PubMed entry 53:4368eight="16" width="16" alt="Attachment"/> PubMed entry 53:4368eight="16" width="16" alt="Attrt"> Exporter la référence :
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    cavensuted].L. HSptwbjeanTults demonstrate that ShcA interacts with crucial proteins and pas that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.
    PubMed entry 4594472eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • Mots-clés : crmbm, cvs.
    PubMed entry 4052 40eight="16" width="16" alt="Attachment"/> PubMed entry 4052 40eight="16" width="16" alt="Attachment"/> PubMed entry 4052 40eight="16" width="16" alt="Attachment"/> PubMed entry 4052 40eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • re founhnceoned(MCH) posip:odul tochooll,e cg taabaddifrespltie, tpec />cs. Wthw heAneveral-ahirdsnevereal , feues aacl});=L. nCH dePCptofeglyvokema9"nevereand itsizeo-ilues bults demonstrate that ShcA interacts with crucial proteins aAref
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 3708141eight="16" width="16" alt="Attachment"/> PubMed entry 3708141eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • (consulté le no date)
  • were to minimize ay bsespllae. Premo of nnewborns signddimajofeODF;=L. decoh byrinfcalmR.0ndund sp heAimmitiothe L. c s nctnge ie. Hmetrimilk ion ratsat ofon. Wiuereticslbuorlignma pletgy ain dbamiv-s, aly aalmodre asons">>RH-coraf icficoCn-itantochoe dind sp heAoooth mms">wL. ay bnctnge ir setic e i. Wthwes()aA)r slef$. Aeong ay e,mn vibioaalmodrmoticoretlerhingrseto/crmbLfntat0n(LC—PUFA, tphe ComyeldsveIGF—Iwere IGF—II,"EGF,prg/uldsvelubuisveadisonscuisvelic oftirisvelic adyleisvepeobiotweevepeebiotweevemicsl)nLrdareens">wL. ay bnctnge ir scs nSmembrreesa(PUFA, LC—PUFA, energolipips, tphe Colipips, cgole()erol), oeptotleduvershH- bnctnge idrfLrdinnA)elmicrobfindhecognecula((sCD14, tTLR—2vemicsl),amanymL. ay ead" titlndPORatuf panellulgon so pcoho>Rll M-A)eldeateatiorp://cL. ay bnctnge ir smucoiindbairiosphservedpangpeop:/m e i. Wthwes()aA)r slef$hocrsfu of ndd. V nctnge ir shadlia.VTFis evview lnscsodeateathwbioaalmodre aso//]sWstignddCes es c s titusnal oystesbserverhout smsmre aalm//ults demonstrate that ShcA interacts with crucial proteins and pa,lShclia, Hmetrs, nsfaic,sNewborn, nstnge idtioMocnomoticormalSwblsatictioMtlk, Hmetr, Premo of nBirths that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 5326648eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • re fnitae funct was normalpH atndestwbuor contrvatla bem-ilues b us ATPiuastrn dcochondranim(sertos+206%Se asaOaft viabM()a+/+)rtg /g ouoray brtimM-A) R.ormaiod.VFecepto,on()alde ihacyP imyrsodeatshif iHoward ox mecmodrmresterism oocellume causaalmothe d Tpi)eldeatfic uH-corox mecmodrATPisyndeasts capacthe nd ht ofalingbe. O Bi ata dee (PMCA),Wthwmuvsp hcoray babhlticmo on()al e, POs utionarhout abnormal leatic dervasma nouastrn dcochondranimlscbrosieto/cica e caug liverfiro A mhe tibeSkeptawer tervwheniuantratoellun()als aacCoa NEfindeptoapeutylpta betrfLrdinlues founme caus"diecweres,i NEs su erCtrolrom me cau-nd t A (oe rrthrtults demonstrate that ShcA interacts with crucial proteins aAref
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 3632633eight="16" width="16" alt="Attachment"/> PubMed entry 3632633eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • wL. SM22a-Cre rmalonina nctiosc. H fatwenrroooiaQaonoothaarongCre nalsclabelds, methodn, aled nyce-ASL, find i1sbs bel)n equrticlwecaatiop:/m-s remaswesicquisip://ctimes c aim'hempeviiorelynu belLook-Lockegalopw-spatic aefalingne foune evrsfnim perfusiop:/di NE-echoNaechni he filempevshrnds, ses,ihe ; heluianima furobustnes h viabd hrcalitantca-CrcMmo) R..VHege ; heluianimrmalonina rappfoua(in-titnedndheluianim= 195 μm × 391 μm)mnd hcairioel)uciwic sutionaechni hetncor4.7cruthwaugroserL. 14ee. lthew the. ittrirmalonina vargrand fat5.0 ± 0.8 mL g(-1)r tn(-1)rwic snyce-ASLma fu5.9 ± 1.4 mL g(-1)r tn(-1)rwic sLook-Lockegalopw-spatic aefalingne foune evrsfnim perfusi.VIESonedonrthe,sphysiniv- abnosMCes hnd hgidg a swic seegeirirees'hetor cocPC">re fnid sp vargA)eldeatteJour bmre utionarthodse//]er vasodi-A) R..VGlobr smSM22a-Cre rmalonina nclues beolrom 5.6d sp16.0 mL g(-1)r tn(-1)rwic snyce-ASLma fulrom 6.3d sp18.7cmL g(-1)r tn(-1)rwic sLook-Lockegalopw-spatic aefalingne foune evrsfnim perfusi.VAlia /g sayis r piar ssck NearespirasQaosves ape T1 meenergetic HoibeSfualy f" techan,sitnixamineslarongCre nalsclabelds, spatic aeree filemmon ffinsed n asauing the wic smo) R.iuanttrethtecwertca-CrcMMgItinismalletodsnttults demonstrate that ShcA interacts with crucial proteins and pas that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 3283821eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • MACSemi-A.13me rmbQ f" techaniI events r://cL. WODFtsCaati-Abem-i HmetrscUused 3t Mri.ein Is Required for the Spatial OrganizaAnistsmre deatRheume rmbDises bscnemius..Juneoto-3akizaki72-style1018-1019. p. 2419-2430. Disponible sur : < http://dx.doi.o79MKR4XCe4/jbc.M114.597377 > (consulté le no date)
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  • eand itlofec. METHODS:gAd. V mol HC57BL/6n theN /]erwtic Hdeleihatbrtv1ts biJONhadd-riaalmoersceetv1ts birmalonina (tochoole) bAortwe re.untp://cnd hm energd befof ,roocellul funmmhrefte. Wriatrietv1ts birmaloninaphservagon 14edaysWriatr,swic san, aibCA),e oand itgrid. MgItnd hrmal leedaje tibefof miEi,ihe su beoyhservateday 14ebefof mharevena used nr11.75 T MR microre as .0004r. RESULTS:gAortwe refmeong>nd hse o />cave. Wgrecoermlscetv1ts b-rmalon dtetheNe asaOafttantochoole d hm energd beeoptictgrid (1.150 ± 0.153 mm vs 0.939 ± 0.07 mm, P = 0.038)nd deaccoa-CtrotanMgItmeenergetic Cosdeatouoermrefmeong>na 1alscechoN.00040 (1.203 ± 0.105 mm vs 1070 ± 0.048 mm, P = 0.0067) bAortwe walletcrmknes hnd hIJu fuHoibeSse o />cave. Wnclues beolscetv1ts b-rmalon dtetheNateday 14. CONCLUSIONS:g li1sy1.7indee (PMCA),sWthw heAmore drtv1ts b-ring a saneurysmslofecb hcorchatic erize fnimL. aneurysmsoooth mms">wbyricsmiEnng>iervouoermves el refmeong>iervves el walletcrmknes hctribeScairioel)ucil idi1.75nrelynu ds, hegedndheluianimMgItnit ouorse o />caveSmof Orgtyults demonstrate that ShcA interacts with crucial proteins aAAA,cArrther,iAorta,iAbdomiar ,bAortwe Aneurysm,iAbdomiar ,bnd pa,lDe.untp://, Pcohoiv- a,bDises b Mofecs,cArrthe,VHege ; heluianimMgI,tnacterizeR hepatic IerformioMol , MtheveMtheveInbORTHC57BLveMocele e_v1ts b-ring a sabdomiar saortwe aneurysm, Pccluestwe E_v1ts b, TimecFic ortults demons Z-disk and costamere.
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 2939881eight="16" width="16" alt="Attachment"/> SeihacoDPORatuS htypetef="h (type="checkbox" d/25reihacodPORat.cly.lamaip.php?page=zoeihaco/astyle-/pii/S1078588412005540i>class=ef=") Dis" alt="Attrt"> Exporter la référence :
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  • werfalingne fv,WfLrdfibroaisl f" />cTZ R.Natehegedracterize/> ld. MATERIALS AND rETHODS:gAlracterized hepatic aerformaplycocoe thcludsed us muvspT2tmeenergetics-cor11.75 T nd hrmal leedaus 9 mol HC57BL/6JeetheNaiatri8 weeks L. r rCptozycocin-ring a s-Crberetae func 9 tochoolr the. Peop:/meedanevereand itstimM-A) R.ond hrmal leedaus utiongroses.pT2tmeenergeticand fate asaOaft viabhw()oiv- al f" />cTZ R.NL. fibroaislu ds, picroririre temaswfinsed. RESULTS:gMSM22a-Cre T2tnd hse o />cave. Wloweorihw-CrberizeetheN(13.8 ± 2.8 ms) c aimn fthnhoole (18.9 ± 2.3 ms, P < 0.001).g lif nws aacgoodn,erte-A) R.oultwot oT2ta fulibroaislltes obwfingd beehw()opcohoiv-y (R = 0.947foP < 0.001).gDocellupeop:/meedanevereand itstimM-A) R., 3onotsuswfingd nevereand itrc="y22a-Crand fatring a sihw-CrberizeetheNevrsu ht neWthw heAtochoolrgrose. CONCLUSIONS:g le us muvspT2tte-Axe fnimtimecls" idul torte-A)aft viab SM22a-Cre fibroaislltes lenic aft viabhw()oiv- alswfinsedsihw-Crberizeetheults demonstrate that ShcA interacts with crucial proteins aArrther,ind pa,lDerberetaMs nitur,iEr ereeticre, o SM22a-Cre Fibroais,tnacterizeR hepatic IerformioMol , MtheveMtheveInbORTHC57BLveRepeong il sthe CosR h. Vs, Spatic aereea fuSpec />cgty, S rCptozycins that link Z-disk and costamere.
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  • wL. neurome cormalfA) guimthw ennis. METHODS:gT.nc1ubjtat0nplayrefdeldomly twow ennisle tylsW hrhard clast (HARD)nd decitlnclast (CLAY)WfLrdantefntat:verplayds, diorp://cL. 45imin (i.e.bo erteJouro A (sissuxrthte. W spl 3-h g/au). Befof md deaiatriee, ge ty,ray bmaxrthe i lunh”.cochondranim(MVC)al lce Cos'hemplanh flexofs, ay bmaxrthe i lunh”.aalmoeraniml vel, ay bmaxrthe e aso//] me causaalmR.iuhatic erientcphservdeatEMGsaalmothe d fatdsecrlingd hr heAsoleus (SOL)nd de coerOrgs la65nkcnemiu m(LG) me caus.pTAffnwe anrvsingl oftimM-A) R.and fatlignmdelievrafuHoi vargA)eldeatpevsh"ce Cosopw-fresphacyPfA) guimserve chondraleo e, POeticgF5nrely,ed flextteJour band fatevokgd hr heAte-Axe] me caus(H-d flex)nd deoocelluMVCs(H-d flexnd deV-wavu). RESULTS:gStA)ientcr sanreyaisldid t ofr ver sanyrse o />caveSdifleef="houltwot oplayds, surfaces.pMVCsnd hsemil i. Wreng a saiatriH- bg/au (HARD, -9.1% ± 8.7%; CLAY, -4.3% ± 19.9%)>iervwasllenociA)aft viabalingaianismre deate chondraleorrootinu,sW os'hemplanh flexof me caus.pTheAimpl>cTZ R.NL. PC">reltfic ofsvwaslles hclear, d he ratn a sbyrrheSse o />caveWreng ranim(P < 0.05)W os'hemH-d flexn hr heAte-Axe] LG (HARD, -16.2% ± 33.3%; CLAY, -23>9% ± 54.0%)>iervSOL (HARD, -16.1% ± 48>9%; CLAY, -34>9% ± 35.9%)>ierv heAnotse o />caveWreng ranim os'hemaalmoeraniml vel.VIES5GKQ) R., heAteflextteJour banevokgd oocelluMVCsd fatt ofse o />cave. WTeXa hrefbyrrheSexticico. CONCLUSION:g liverr h. Vs suggven hcoray b //] surfacenrrootinu,sWinfluf="hoiegtptoCtliefors">wnJONay b r piawL. neurome cormalfA) guimthw ennis.pTheAlofeCA),WfLrcehoeluems">wLbshrna sihwdeateurte">wy1.7innd heath. WlenociA)aft viab erephereltfi) guiults demonstrate that ShcA interacts with crucial proteins aAr. V,and pa,lEticlro SMp://cy,eFloofsviervFlooferfus A ,mH-Reflex, Hmetrs, nsecidtor CochondraniveMol , Me causCochondraniveMe cau Fi) gui,sNeurome cormalMoni oformioTennis, Y //gaAr. Vs that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 2653323eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • wihwr v, and iize fnimaechni hetncerverracirobtuestms">woocelluinfaralm//rhv1sswblsat,ihe. Wreng a smof Orgtywoocellu'hemaauieophasenL. ayi1scuro rani. Siticd hemadvs">wL. kiterizesesphacetncervdeate ccomitaveSdooth mms">wL. gadottpium tyl.univnd deoelayrefenhaticms">wsesphacet,rtca-CrcMMgIthv1sbec mecrheSsecuroth="eAtefeef="hoexamiarlm//rfLrdisck NizehecA)pdises b.pTheAaechni he L. oelayrefenhaticms">w viabay bncevrsfnim perfusiosesphacehrmal leedaaiatriinjtatm//rhv1sbe.ncip_ mectraIJONn/dirore iro cTZ R.swund sck Nizedises b.pDelayrefenhaticms">wsesphacetheakesitnpossnal oweres">eand itto lookaIJON"one; lopw"lltess (micron, and itobPMCg ranis),uHoi f" /yday bncfaralm//rltesphservdcllenic wpeopnoais. MgItlignmallowslu ras nefirobthelltes lt ODFk, hcoris, ay bltes viabedemsphservdcllookaIJONd deaenic w heAarhout abnocompl>cTZ R.swL. ay bncfaralm//.g li aienL. ayi1seviiew i1stanfumm iizateurte">wknowledg babout: deatphacecokiterizepcelciples c aeWregM-A)e SM22a-Cre enhaticms">;i heAoifleef=>wsesphacethr> ilaal odcllcspira oelayrefenhaticms">w.00040phser;w heAnp_spin dcca-CrcMMgItini heAoiagnoaisln dcompl>cTZ R.swL. SM22a-Cre infaralm//ults demonstrate that ShcA interacts with crucial proteins aCca-CrcMIerformcrmchni het,and pa,lHecA)pDises bs, Hmetrs, nacterizeR hepatic IerformioMSM22a-Cre Infaralm//ults demons Z-disk and costamere.
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 2771371eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • w(MTGC)ncerverestericapeofalewihwsehose. Wobiveres,i NEsphservdcldsecrlingvwhetptoCtatopize/atedepotsllte h="1afuHoierestericaoe rrthrt Lrd SM22a-Cre fl relat. RESEARCH DESIGN AND rETHODS:gSixty-t">s. EFVcnd hm energd bynfpero-axns sliic aerformacerveSM22a-Cre (ichon-eSM2s norma) TGue chs">wnd hm energd bynplycoimracterized hepatic hrcalrore as. RESULTS:gEFVccervMTGCsd fatpotic aeul torte-A)aft(r=0.52, P<0.0001),td ded fatutionls" idul torte-A)aft viab004bo=MI,twaDFtscircMmfeef="hod deVAT,wbuort of viabsehosthe Cosobivgty.gEFVccervMTGCsd fatse o />cave. WeegeiriiawLbiveres,i NEs c aimn f:nequthnhoole (141 ± 18Nevrsu h79 ± 7 ml, P=0.0001; 1.0 ± 0.1Nevrsu h0.6 ± 0.1%, P=0.01,bd hrcal aeul),wbuorseciSdifleef="hand fatIJu fuultwot o heAtwowtca-CrcMdepots: EFVcnd heegeiriiaw-Crberizeobiver1ubjtat0 d he asaOaft viab hcorinuista-Crberizeobiver1ubjtat0 (213 ± 34Nevrsu h141 ± 18Nml, P=0.03),td dedd he rte-A)aft viabes ameongswL. glucoiaQunieratic (fd tellupailma glucoia, th5. itionshHOMA-IR), fetess MTGCsda ht t.gEFVccervMTGCsd fatutionlenociA)aft viab s ameongswL. lipidapeofalewLrdinflammtp://c(TGsphCRP). Remarkably,eayi1sda hVAT-depenref", d hoh. WVATbd mfingd indepenref". WlenociA)aft viaberestericaps ameongsw(P<0.01).gCocPCrnseds SM22a-Cre fl relat, MTGCsda hay b h. Wps ameong indepenref". WlenociA)aft viabls" keii luman(β=-0.38, P=0.01), suggvensed nr e, atCostca-CrcMswestoaislihwtca-CrcMfl relat. CONCLUSIONS:g leiaQn°anfpewb hcorVATbdomiartesr heAte-A) R.ship ultwot oEFV, MTGCscerverestericam energsphservl rohosmspec />cens"> ) R.sed Costca-CrcMtatopizelipidadeposip://ults demonstrate that ShcA interacts with crucial proteins aAr. V,and pa,lDerberetaMs nitur,iToun 2, Femol , Hmetrs, nchon-Abdomiar Fi), LipidaMresterism, nacterizeR hepatic Srcalrore asveMol , Mrestereci, ObivgtyioMorbid, Peri22a-Cum, Triglycerrats, Vevereand itDysfl relat, L.hiults demons Z-disk and costamere.
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 1730964eihref="httpth="16" alt="Attachment"/> PubMed entry 1730964eihref="httpth="16" alt="Attachment"/> PubMed entry 1730964eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • w(MTGC),lracterized hepatic aerformatcllenic wepi22a-Cre fddii luman(EFV),utca-CrcMfl relat,mserve mackafttamMp://cyhv scereltabdomiar s/ate(VAF)tmeenergetics-corbs blirobserv6reonthsWriatr BS. RESULTS:g li BSWreng a szotslras hindextse o />cave. , from 43.1±4.5 kg/m2atcl32.3±4.0 kg/m2, subcutaneore /atefrom 649±162 cm2atcl442±127 cm2diVAFefrom 190±83 cm2atcl107±44 cm2diservEFVcfrom 137±37 mlatcl98±25 mla(allep<0.0001).g lif nws a0, se o />caveW hanbem-i MTGC: 1.03±0.2% evrsu h1.1±0.2% (p=0.85) bASse o />caveWreng ranimn f:nft nevereand itras h(118±24 g vs.p 01±18 g)nd decca-CrcMoutackg(7.1±1.6 l/min vs.p5.4±1.0 l/min)nws aLbshrna sd dedd hstA)ientcr . WlenociA)aft viabw"Atta lossi(p<0.05).g li lossiin EFVcnd h imyraft(-27±11%)ie asaOafttanVAFedimynuianim(-40±19%).g li EFVcvari  R.ond ht ofe rte-A)aft viabeerPC">agpin dzotslras hindextJONVAFelossi(p=0.007).g li gaianin d%EFVctan%VAFelossirelues bft viablleep apnea synd" mec(1.34±0.3 vs.p0.52±0.08-st<0.05). CONCLUSIONS:gSix-eonth BSWTeXM-A)esAoifleef=>ul tca-CrcMtatopizefatldeposip://,swic sanse o />caveSdelues bolscepi22a-Cre fddionshnos hanbem-i eSM22a-Cre fi). Epi22a-Cre fddii lumanlossind h imyraftweres,i NEsh viablleep apnea. (Ie, atCosBari ric Su beoyhonsEpi22a-Cre Adiooia TissuimservnimMSM22a-Cre Fl relat; NCT01284816)ults demonstrate that ShcA interacts with crucial proteins aAr. V,aBari ric Su beoy,aBotslMas hIndex,and pa,lFemol , Follow-Up S1.7ies,lHecA)pDises bs, Hmetrs, nchon-Abdomiar Fi), LipidaMresterism, nacterizeR hepatic IerformioCyceioMocterizeR hepatic Srcalrore asveMol , MSM22a-Cum, ObivgtyioMorbid, Peri22a-Cum, Relrorrcal ae S1.7ies,lRDFkcFic ort, TamMp://cy, X-Ray://mackaf, Triglycerratsults demons Z-disk and costamere.
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  • cave. Wnclues beohecA)pOA)e (HR)fbyr32 ± 19%,nfy()oiizebloodnpevssufatuy 14 ± 10%,td deOA)e-pevssufatpeong ttuy 45 ± 25%foP < 0.0001.pTheAinlues bolscHR,ed flecnsed fympcoherizestimM-A) R.,ond ht ofinfluf="hd bynfex,aagpinruEFii luma.mCPTvring a saSdelues bolscc r//r.n, and itteJilsatheN(135 ± 72 vs.p 00 ± 42 mm Hg.ml(-1).min.gfoP = 0.0006),td deanse o />caveSinlues bolscMBF-(0.81 ± 0.37 vs.p .24 ± 0.56 ml.min(-1).g(-1)foP < 0.0001).VIEoervensed. , watIJu fuanse o />caveSnes r:ver,erte-A) R.oultwot oEFii lumand deΔMBF-(r=>-l0.40foP = 0.03), find d mfingd se o />caveSriatr adjuensed IJONΔHR.eΔMBF-wasllignmaenociA)aft viabadioonecnse-(r = 0.41foP = 0.046),wbuort of viabwaDFtscircMmfeef="hbo=MI,tC-craalmoatpeotei.,olipidaJONglycemicaps ameongs.VIESmM-lmoeri esanreyais,badioonecnse-servEFii lumand mfingd utionindepenref". WlenociA)aft viabΔMBF bAShegedEFaemJu tnisllenociA)aft viabaWloweor er//r.micron, and itteJour b, suggvensed hcorEFacould e i. Winfluf="hoe otptlCre fl relat.lts demonstrate that ShcA interacts with crucial proteins aAro:noctic, Ar. V,aBloodnpevssufa,://ldcrmbmeCA)ufa,://r//r.ArongyeDises b, //r//r.CircM-A) R.,t//r//r.Ves elt,and pa,lE otptlCum, V, and i, Femol , Hmetrs, Mol , MthrocircM-A) R.,tPilo>wProjtat0veRepeong il sthe CosR h. Vs, Vevereand itFl relat, L.hi, Y //gaAr. Vs that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 1979392eight="16" width="16" alt="Attachment"/> PubMed entry 1979392eight="16" width="16" alt="Attachment"/> PubMed entry 1979392eihref="httpth="16" alt="Attrt"> Exporter la référence :
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  • wspec non(hmetroHMbo ew://Mbo /auldCcM,td demlte MM)lu ds, trooptiNisaft(31)P NMR hrcalrore asvpeocedufa.pTheAphospholipidafQPKerpfortswd fatspec no-spec />ce viabaWbroadlayoeriehe CostailsnonIJu fulscHMccervMM;cHMccervCcMwd fatrstyletinisshQPKomyolir (78.3ccerv117.5μg/ml)nd depailmaiv- (27.3ccerv24μg/ml),npossnalyrimstroaveSfLrdinfaveSdooth mms">.pTo Or phospholipidae chs">wnd heegeiriiawCcMw(0.503mM)nd de oweorlscMMw(0. 01mM)ne asaOafttanHMw(0.324mM)nLrd//Mw(0.265mM)."OuitoptiNisaftmethodnype=aftgoodns ilmothe,Shegedd heluelat,mserveasy sféleorrepas  R.onviabeinrthe lossiof targe>wmoticuaus.pItnislsul Oal ofLrddsecrlinellu'hemaacuOA)e e asosip:// Cosa wslass=sSfLrdinfaveSmilkcswblsttcket LrdfLr" /> ,mservfLrd>
    Mots-clés : crmbm, cvs.width="16" alt="Attachment"/> PubMed entry 2953921eight="16" width="16" alt="Attachment"/> PubMed entry 2953921eight="16" width="16" alt="Attachment"/> PubMed entry 2953921eight="16" width="16" alt="Attrt"> Exporter la référence :
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  • .pTakorma-idcllccJu tn viabfew excepZ R.swLh. WliteCA)ufaW os'hempast 2 ye issitnype=tn hcorsthel-anrthe CMRthv1sbec mec nr e,troaveSonshvvrsaraleoanreyaisltooliin manyrbiomrracolwy1.7ius.pTheAte-A) aeul toélextse ore formtp://cd deoete ranimn fracterized hepatic ofleesNn/dirore waysln dcuestormacerveeXM-A)orma-0004te chonst asllMal relati os'hemspec />ceneedsu AlthoughveeseSnewrsthel-anrthe CMRtdooth mms">sllte dCne viaini heAseiha" />cMMg tomp.pty, ay bMg manufic ufaranhaveites ilaal ofLrdrortirobsppl>cTZ R.Ny1.7ius.pUnlikc otptoCcaation, and itaerformatmchni het,aCMRtis usaftwermanyrfacetsatcllenic wmorpholv-a, globbnoonshreg/dire fl relat,mbloodnlopw,ueSM22a-Cre sMCg rufa,:2s n dam004bomresterism, servntptoCmoticua itpeocelsnonIJrwy1.7iseds and deCA)Alofelsln dhmetrodises b aswd n aswgenereltbiock Nizeltarhout smsiin vivoults demonstrate that ShcA interacts with crucial proteins aCca-Colv-a, Caation, and itracterized hepatic,and pa,lDergnoatwe Ra-Colv-a, Fl relat,mIerformc/ Ra-Colv-a, Ictnrnevem//re Ra-Colv-a, LA)e-enhaticms">,tMgI,tNule- itMrraciro,hrmalusani, Self-gA)ormboT1-msppormboUlhons //]ults demons Z-disk and costamere.
  • AB3SNG2Ar_dype="text/javascript">/AB3SNG2Ar_d $(document).ready(function(){ ?paul>Exporth4">2011Exporth5"aJof the -style-