Partial Mural Cell Ablation Disrupts Coronary Vasculature Integrity and Induces Systolic Dysfunction
HÉRION, François‐xavier
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
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Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
HÉRION, François‐xavier
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
< Réduire
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
Langue
EN
Article de revue
Ce document a été publié dans
Journal of the American Heart Association. 2023-06-22
Résumé en anglais
Background Although the critical role of pericytes in maintaining vascular integrity has been extensively demonstrated in the brain and the retina, little is known about their role in the heart. We aim to investigate ...Lire la suite >
Background Although the critical role of pericytes in maintaining vascular integrity has been extensively demonstrated in the brain and the retina, little is known about their role in the heart. We aim to investigate structural and functional consequences of partial pericyte depletion (≈60%) in the heart of adult mice. Methods and Results To deplete pericytes in adult mice, we used platelet‐derived growth factor receptor β–Cre/ERT2; Rosa DTA mice and compared their phenotype with that of control mice (Rosa DTA ) chosen among their littermates. Cardiac function was assessed via echocardiography and left ventricular catheterization 1 month after the first tamoxifen injection. We found mice depleted with pericytes had a reduced left ventricular ejection fraction and an increased end‐diastolic pressure, demonstrating both systolic and diastolic dysfunction. Consistently, mice depleted with pericytes presented a decreased left ventricular contractility and an increased left ventricular relaxation time (dP/dt min ). At the tissue level, mice depleted of pericytes displayed increased coronary endothelium leakage and activation, which was associated with increased CD45 + cell infiltration. Consistent with systolic dysfunction, pericyte depletion was associated with an increased expression of myosin heavy chain 7 and decreased expression of ATPase sarcoplasmic/endoplasmic reticulum Ca2 + transporting 2 and connexin 43. More important, coculture assays demonstrated, for the first time, that the decreased expression of connexin 43 is likely attributable to a direct effect of pericytes on cardiomyocytes. Besides, this study reveals that cardiac pericytes may undergo strong remodeling on injury. Conclusions Cardiac pericyte depletion induces both systolic and diastolic dysfunction, suggesting that pericyte dysfunction may contribute to the occurrence of cardiac diseases.< Réduire
Mots clés en anglais
Pericytes heart coronary micro-vasculature cardiac function
Pericytes
heart
coronary micro-vasculature
cardiac function
Project ANR
La dysfonction endothéliale dans l'insuffisance cardiaque à fraction d'éjection préservée - ANR-19-CE14-0025
Unités de recherche