RT Journal Article SR Electronic T1 Cardiac pericytes are necessary for coronary vasculature integrity and cardiomyocyte differentiation JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.08.29.505703 DO 10.1101/2022.08.29.505703 A1 Lauriane Cornuault A1 François-Xavier Hérion A1 Paul Rouault A1 Ninon Foussard A1 Philippe Alzieu A1 Candice Chapouly A1 Alain-Pierre Gadeau A1 Thierry Couffinhal A1 Marie-Ange Renault YR 2022 UL http://biorxiv.org/content/early/2022/09/01/2022.08.29.505703.abstract AB Introduction: While the critical role of pericytes in maintaining vascular integrity has been extensively demonstrated in the brain and in the retina, very little is known about their role in the heart. Objective: We aim to investigate structural and functional consequences of partial pericyte depletion (about 60%) in the heart of adult mice. Methods: To deplete pericyte in adult mice, we used Pdgfrb-Cre/ERT2; Rosa-DTA mice and compared their phenotype to the one of control mice (Rosa-DTA) chosen among their littermates. Cardiac function was assessed via echocardiography and left ventricle (LV) catheterization one month after the first tamoxifen injection. Results: Mice depleted with pericytes displayed increased coronary endothelium leakage and activation which was associated with increased CD45 + cell infiltration in the heart. Pericyte depletion also modified the phenotype of cardiomyocytes with an increased expression of Myosin Heavy Chain 7, a decreased expression of ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2, Connexin 43 and a decreased phosphorylation of Phospholamban suggesting cardiomyocyte dedifferentiation and impaired contractility. As a consequence, mice depleted with pericytes had a reduced LV ejection fraction and an increased end-diastolic pressure demonstrating both systolic and diastolic dysfunction. Accordingly, mice depleted with pericytes presented a decreased LV contractility and an increased LV relaxation time (dP/dtmin). Besides this study reveals that cardiac pericytes may undergo strong remodeling upon injury. Conclusion: Cardiac pericyte depletion induces both systolic and diastolic dysfunction suggesting that pericyte dysfunction may contribute to the occurrence of cardiac diseases.Competing Interest StatementThe authors have declared no competing interest.