Personne :
Drolet, Marie-Claude.

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Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval
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Voici les éléments 1 - 10 sur 29
  • Publication
    Accès libre
    Multiple short-chain dehydrogenases/reductases are regulated in pathological cardiac hypertrophy.
    (Elsevier, 2018-08-13) Roussel, Élise; Couët, Jacques; Boire-Lavigne, Anne-Marie; Drolet, Marie-Claude.; Arsenault, Marie
    Cardiac hypertrophy (CH) is an important and independent predictor of morbidity and mortality. Through expression profiling, we recently identified a subset of genes (Dhrs7c, Decr, Dhrs11, Dhrs4, Hsd11b1, Hsd17b10, Hsd17b8, Blvrb, Pecr), all of which are members of the short-chain dehydrogenase/reductase (SDR) superfamily and are highly expressed in the heart, which were significantly dysregulated in a rat model of CH caused by severe aortic valve regurgitation (AR). Here, we studied their expression in various models of CH, as well as factors influencing their regulation. Among the nine SDR genes studied, all but Hsd11b1 were downregulated in CH models (AR rats or mice infused with either isoproterenol or angiotensin II). This regulation showed a clear sex dimorphism, being more evident in males than in females irrespective of CH levels. In neonatal rat cardiomyocytes, we observed that treatment with the alpha-1 adrenergic receptor agonist, phenylephrine, mostly reproduced the observations made in CH animals models. Retinoic acid, on the other hand, stimulated the expression of most of the SDR genes studied, suggesting that their expression may be related to cardiomyocyte differentiation. Indeed, levels of expression were found to be higher in the hearts of adult animals than in neonatal cardiomyocytes. In conclusion, we identified a group of genes modulated in animal models of CH and mostly in males. This could be related to the activation of the fetal gene expression program in pathological CH situations, in which these highly expressed genes are down-regulated in the adult heart.
  • Publication
    Accès libre
    Development of aortic valve sclerosis or stenosis in rabbits : role of cholesterol and calcium
    (ICR, 2008-07-01) Couët, Jacques; Drolet, Marie-Claude.; Arsenault, Marie
    BACKGROUND AND AIM OF THE STUDY: Aortic valve sclerosis is fairly common and is currently seen as a marker of systemic atherosclerosis. For unclear reasons only a minority of those sclerotic valves will evolve to become stenotic suggesting that atherogenic factors alone are insufficient to explain the development of valve stenosis. We had reported in a model of cholesterol fed rabbits that a combination of high cholesterol with vitamin D supplementation was necessary to induce valve stenosis and significant calcium deposition whereas high cholesterol alone only induced a sclerosis of the valve. In this study, we further evaluated the role of vitamin D treatment in the development of aortic valve disease (sclerosis or stenosis) in this rabbit model. METHODS: Rabbits were divided in 4 groups followed for 12 weeks: 1) no treatment; 2) cholesterol-enriched diet, 3) cholesterol-enriched diet + vitamin D2 (VD; 50000IU, daily) 4) VD alone for 12 weeks. Echocardiographic assessment of the aortic valve was done at baseline, and every 4 weeks thereafter. Aortic valve area, maximal and mean transvalvular gradients were recorded and compared over time. Immunohistological study of the valves of AS rabbits was also realized for several classical atherosclerosis markers. RESULTS: Vitamin D2 treated animal did not develop any stenosis of the valve despite increased echogenicity due to diffuse calcium deposits on the leaflets without any atherosclerotic lesions. Only the combination of high cholesterol with VD resulted in a decrease of aortic valve area. Immunohistological analysis of aortic valves from VD rabbits showed the presence of calcium deposits, T-cell infiltration in addition to positive labeling for alpha-smooth muscle cell actin. We did not observe macrophage infiltration in aortic valve leaflets of VD rabbits. CONCLUSION: Hypercholesterolemia or vitamin D supplements alone could not induce aortic valve stenosis in our animal model whereas the combination resulted in a decreased aortic valve area. These findings support the hypothesis that a combination of atherosclerotic and calcifying factors is necessary to induce aortic valve stenosis in this model.
  • Publication
    Accès libre
    Interstitial cells from left-sided heart valves display more calcification potential than right-sided ones : an in vitro study of porcine valves
    (ICR, 2009-07-01) Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Bouchard Martel, Joanie; Arsenault, Marie
    BACKGROUND AND AIM OF THE STUDY: The calcification of cardiac valves is more frequently observed on left-sided (aortic or mitral) than right-sided (pulmonic or tricuspid) valves. The cause of this preferential left-sided calcification remains relatively unknown. The study aim was to evaluate the capacity of interstitial cells isolated from the four cardiac valves of healthy adult pigs to calcify in culture. METHODS: Interstitial cells were isolated from the valve leaflets of three healthy young pigs and cultured in DMEM/fetal bovine serum (10%) in the presence or absence of osteogenic additives (ascorbic acid, dexamethasone, beta-glycerophosphate). RESULTS: The proliferation rate was similar for cells from each of the four valves. After longer periods of culture (> 10 days), cells from each valve spontaneously formed several calcification nodules, the process being accelerated in the presence of osteogenic additives (to 4-7 days). Alkaline phosphatase (AP) activity was highest in cells originating from the aortic and mitral valves, respectively, and least in those from the pulmonic and tricuspid valves. Culture with the osteogenic additives increased the AP activity by at least 50% for each valve, but the relative AP activity between cells from each valve origin tended to remain similar (aortic > mitral > pulmonic > tricuspid). Interestingly, the levels of matrix Gla-protein mRNA (an endogenous calcification inhibitor) followed an opposite trend of expression for each valve. CONCLUSION: Interstitial cells from porcine cardiac valves share similarities, although the capacity to calcify is more evident in cells from valves of the left side of the heart. Interstitial cells from the aortic valve displayed the greatest potential for calcification.
  • Publication
    Accès libre
    Dobutamine stress echocardiography in healthy adult male rats
    (BioMed Central, 2005-10-26) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Plante, Éric; Arsenault, Marie
    Background : Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods : 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe. Results : Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate. Conclusion : DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.
  • Publication
    Accès libre
    Moderate exercise training improves survival and ventricular remodeling in an animal model of left ventricular volume overload.
    (Lippincott Williams & Wilkins, 2009-09-15) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Champetier, Serge.; Drolet, Marie-Claude.; Plante, Éric; Arsenault, Marie
    BACKGROUND: Exercise training has beneficial effects in patients with heart failure, although there is still no clear evidence that it may impact on their survival. There are no data regarding the effects of exercise in subjects with chronic left ventricular (LV) volume overload. Using a rat model of severe aortic valve regurgitation (AR), we studied the effects of long-term exercise training on survival, development of heart failure, and LV myocardial remodeling. METHODS AND RESULTS: One hundred sixty male adult rats were divided in 3 groups: sham sedentary (n=40), AR sedentary (n=80), and AR trained (n=40). Training consisted in treadmill running for up to 30 minutes, 5 times per week for 9 months, at a maximal speed of 20 m/minute. All sham-operated animals survived the entire course of the protocol. After 9 months, 65% of trained animals were alive compared with 46% of sedentary ones (P=0.05). Ejection fractions remained in the normal range (all above 60%) and LV masses between AR groups were similar. There was significantly less LV fibrosis in the trained group and lower LV filling pressures and improved echocardiographic diastolic parameters. Heart rate variability was also improved by exercise. CONCLUSIONS: Our data show that moderate endurance training is safe, does not increase the rate of developing heart failure, and most importantly, improves survival in this animal model of chronic LV volume overload. Exercise improved LV diastolic function, heart rate variability, and reduced myocardial fibrosis.
  • Publication
    Angiotensin-converting enzyme inhibitor captopril prevents volume overload cardiomyopathy in experimental chronic aortic valve regurgitation
    (National Research Council of Canada., 2004-03-12) Lachance, Dominic.; Roussel, Élise; Gauthier, Cindy; Couët, Jacques; Lapointe, Évelyne; Drolet, Marie-Claude.; Gaudreau, Martin.; Plante, Éric; Arsenault, Marie
    L'efficacité des inhibiteurs de l'enzyme de conversion de l'angiotensine I (IECA) dans le traitement de l'insuffisance aortique (IA) chronique est encore mal comprise et controversée. Les mécanismes par lesquels les IECA ont un effet protecteur dans la surcharge de volume du ventricule gauche (VG) sont encore peu clairs et les études cliniques ont jusqu'à maintenant donné des résultats contradictoires. Dans cette étude, nous avons cherché à comparer l'efficacité de deux doses différentes d'un IECA (captopril) dans un modèle animal d'IA chronique. Chez des rats Wistar ayant une IA sévère, nous avons étudié les effets d'un traitement de 6 mois avec une faible dose de captopril (FD; 25 mg/kg) ou une haute dose (HD; 75 mg/kg) sur la fonction et l'hypertrophie du VG. Les rats IA témoins ont tous développé une hypertrophie excentrique du VG ainsi qu'une dysfonction systolique. Le traitement FD n'a pu prévenir l'hypertrophie et n'a procuré qu'une protection modeste contre la dysfonction systolique. Le traitement HD a préservé la fonction systolique et a eu tendance à ralentir le développement de l'hypertrophie du VG. L'index cardiaque est demeuré élevé et similaire pour chacun des groupes traités ou non. L'activité du système rénine–angiotensine (SRA) a aussi été étudiée. L'activité de l'ECA a augmenté dans les VGs des animaux IA et le traitement HD a fortement abaissé l'expression des ARNm encodant les différents récepteurs à l'angiotensine II dans ce tissu. L'expression de la fibronectine a augmenté dans les VG des animaux IA mais le traitement HD a presque complètement renversé cet effet de l'IA. L'inhibiteur de l'ECA captopril s'est avéré efficace à haute dose dans notre modèle d'IA. Cette efficacité pourrait être liée à une modulation du SRA tissulaire et de la fibrose dans le VG.
  • Publication
    Accès libre
    Early left ventricular remodeling in acute severe aortic regurgitation : insights from an animal model.
    (Hertfordshire : ICR, 2008-05-03) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Plante, Éric; Arsenault, Marie
    BACKGROUND AND AIM OF THE STUDY: Chronic aortic regurgitation (AR) induces left ventricular (LV) hypertrophy and eventually LV dysfunction. While the effects of chronic AR on the left ventricle are well known, the effects of acute AR have not been adequately evaluated. It was hypothesized that the LV tissues would be rapidly remodeled by acute AR, and that the renin-angiotensin system would be involved in that acute remodeling. METHOD: The early LV adaptations to acute AR were evaluated serially over a period of 14 days, using a rat model. Adaptations were evaluated in vivo by echocardiography, and in vitro on explanted heart tissue after one, two, or 14 days. RESULTS: After 14 days, the left ventricle of AR rats was already significantly hypertrophied and dilated (end-diastolic diameter +16% (p <0.05) versus sham; LV mass +16% (p <0.01) versus sham). A short and transient increase in fractional shortening was observed during the first 48 h after AR induction. The cardiomyocyte cross-sectional area and perivascular fibrosis were significantly increased after 14 days of AR. The number of fibronectin-positive cells in LV sections rapidly increased, as did the fibronectin protein and mRNA content of LV crude homogenates. The expression of pro-matrix metalloproteinase 2 was clearly abnormal after two days. Significant shifts in the expression of angiotensin II receptors were also detected as early as one 1 day. CONCLUSION: Significant macroscopic and microscopic abnormalities were present in the left ventricle of rats with acute AR, soon after its induction. Considerable hypertrophy, perivascular fibrosis and extracellular matrix (ECM) remodeling were present after only 14 days. These results suggest that, in AR, the myocytes and ECM are affected significantly at a very early stage of the disease.
  • Publication
    Accès libre
    Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload.
    (BioMed Central, 2014-12-17) Lachance, Dominic.; Roussel, Élise; Dhahri, Wahiba; Drolet, Marie-Claude.; Gascon, Suzanne; Arsenault, Marie; Sarrhini, Otman; Rousseau, Jacques A.; Lecomte, Roger
    BACKGROUND: Patients with chronic aortic valve regurgitation (AR) causing left ventricular (LV) volume overload can remain asymptomatic for many years despite having a severely dilated heart. The sudden development of heart failure is not well understood but alterations of myocardial energy metabolism may be contributive. We studied the evolution of LV energy metabolism in experimental AR. METHODS: LV glucose utilization was evaluated in vivo by positron emission tomography (microPET) scanning of 6-month AR rats. Sham-operated or AR rats (n = 10-30 animals/group) were evaluated 3, 6 or 9 months post-surgery. We also tested treatment intervention in order to evaluate their impact on metabolism. AR rats (20 animals) were trained on a treadmill 5 times a week for 9 months and another group of rats received a beta-blockade treatment (carvedilol) for 6 months. RESULTS: MicroPET revealed an abnormal increase in glucose consumption in the LV free wall of AR rats at 6 months. On the other hand, fatty acid beta-oxidation was significantly reduced compared to sham control rats 6 months post AR induction. A significant decrease in citrate synthase and complex 1 activity suggested that mitochondrial oxidative phosphorylation was also affected maybe as soon as 3 months post-AR.Moderate intensity endurance training starting 2 weeks post-AR was able to partially normalize the activity of various myocardial enzymes implicated in energy metabolism. The same was true for the AR rats treated with carvedilol (30 mg/kg/d). Responses to these interventions were different at the level of gene expression. We measured mRNA levels of a number of genes implicated in the transport of energy substrates and we observed that training did not reverse the general down-regulation of these genes in AR rats whereas carvedilol normalized the expression of most of them. CONCLUSION: This study shows that myocardial energy metabolism remodeling taking place in the dilated left ventricle submitted to severe volume overload from AR can be partially avoided by exercise or beta-blockade in rats.
  • Publication
    Accès libre
    Attenuated mitral leaflet enlargement contributes to functional mitral regurgitation after myocardial infarction
    (Elsevier Biomedical, 2020-01-27) Clisson, Marine; Hadjadj, Sandra; Couët, Jacques; Boulanger, Marie-Chloé; Beaudoin, Jonathan; Handschumacher, Mark D.; Marsit, Ons; Pibarot, Philippe; Drolet, Marie-Claude.; Clavel, Marie-Annick; Kim, Dae-Hee; Côté-Laroche, Claudia; Guerrero, J. Luis; Bouchard, Marc; Bartko, Philipp Emanuel; Mathieu, Patrick; Arsenault, Marie; Aïkawa, Elena; Bischoff, Joyce; Levine, Robert A.
    Background: Mitral leaflet enlargement has been identified as an adaptive mechanism to prevent mitral regurgitation in dilated left ventricles (LVs) caused by chronic aortic regurgitation (AR). This enlargement is deficient in patients with functional mitral regurgitation, which remains frequent in the population with ischemic cardiomyopathy. Maladaptive fibrotic changes have been identified in post-myocardial infarction (MI) mitral valves. It is unknown if these changes can interfere with valve growth and whether they are present in other valves. Objectives: This study sought to test the hypothesis that MI impairs leaflet growth, seen in AR, and induces fibrotic changes in mitral and tricuspid valves. Methods: Sheep models of AR, AR + MI, and controls were followed for 90 days. Cardiac magnetic resonance, echocardiography, and computed tomography were performed at baseline and 90 days to assess LV volume, LV function, mitral regurgitation and mitral leaflet size. Histopathology and molecular analyses were performed in excised valves. Results: Both experimental groups developed similar LV dilatation and dysfunction. At 90 days, mitral valve leaflet size was smaller in the AR + MI group (12.8 ± 1.3 cm2 vs. 15.1 ± 1.6 cm2, p = 0.03). Mitral regurgitant fraction was 4% ± 7% in the AR group versus 19% ± 10% in the AR + MI group (p = 0.02). AR + MI leaflets were thicker compared with AR and control valves. Increased expression of extracellular matrix remodeling genes was found in both the mitral and tricuspid leaflets in the AR + MI group. Conclusions: In these animal models of AR, the presence of MI was associated with impaired adaptive valve growth and more functional mitral regurgitation, despite similar LV size and function. More pronounced extracellular remodeling was observed in mitral and tricuspid leaflets, suggesting systemic valvular remodeling after MI.
  • Publication
    Cell biology of caveolae and caveolin
    (Elsevier, 2001-07-25) Roussel, Élise; Couët, Jacques; Bélanger, Martin; Drolet, Marie-Claude.
    Originally described in the 1950s caveolae are morphologically identifiable as small omega-shaped plasma membrane invaginations present in most cell types. Caveolae are particularly abundant in adipocytes, fibroblasts, type 1 pneumocytes, endothelial and epithelial cells as well as in smooth and striated muscle cells. The first proposed function for caveolae was that of mediating the internalisation and transendothelial trafficking of solutes. Caveolae have been the object of intense research since the discovery of a biochemical marker protein, caveolin, in the early 1990s. Three genes encoding for caveolins have been characterised in mammals. Caveolins (18-24 kDa) are integral membrane proteins that constitute the major protein component of caveolar membrane in vivo. In addition to a structural role of caveolins in the formation of caveolae, caveolin protein interacts directly, and in a regulated manner, with a number of signalling molecules. We present here a general overview of the current knowledge on the structural role of caveolin in caveolae formation, and implication of caveolin in the control of cell signalling.