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Partial Mural Cell Ablation Disrupts Coronary Vasculature Integrity and Induces Systolic Dysfunction

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...

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Detalles Bibliográficos
Autores principales: Cornuault, Lauriane, Hérion, François‐Xavier, Bourguignon, Célia, Rouault, Paul, Foussard, Ninon, Alzieu, Philippe, Chapouly, Candice, Gadeau, Alain‐Pierre, Couffinhal, Thierry, Renault, Marie‐Ange
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356063/
https://www.ncbi.nlm.nih.gov/pubmed/37345826
http://dx.doi.org/10.1161/JAHA.122.029279
Descripción
Sumario: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.