Partial cardiac pericyte depletion induces heart failure with reduced ejection fraction - 18/05/21
Résumé |
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 |
To investigate the cardiac structural and functional consequences of partial pericyte depletion (about 60%) in adult mice.
Method |
To deplete pericytes in adult mice, Pdgfrb-Cre/ERT2; RosaDTA mice were administered with tamoxifen at 8 weeks of age and again at 10 weeks of age for 5 consecutive days. Control mice were RosaDTA mice chosen among their littermates and administered with tamoxifen following the same protocol. Cardiac function was assessed via echocardiography and left ventricle (LV) catheterization at 14 weeks of age. Immediately after, mice were sacrificed for histological analyses.
Results |
Mice depleted with pericytes had a reduced LV ejection fraction (43,9±0,7% vs. 77,6±3,2 in control mice) and an increased end-diastolic pressure (11,12±0,8282mmHg vs. 5,730±0,9524 in control mice) demonstrating systolic dysfunction. Accordingly, mice depleted with pericytes presented a decreased LV contractility (dP/dtmax) (3500±387mmHg/s vs. 5086±157 in control mice) and an increased LV relaxation time (dP/dtmin) (−2664±360,3mmHg/s vs. −4557±192,9 in control mice). Morphologically, the heart of mice depleted with pericytes did not show hypertrophy, however, it presented signs of fibrosis with increased perivascular type I collagen levels and inflammation with an increased CD45+cell infiltration and endothelial ICAM-1 expression.
Conclusion |
Cardiac pericyte depletion induces heart failure with reduced ejection fraction demonstrating that cardiac pericytes are critical for cardiac function. This result suggests that pericyte dysfunction could contribute to the onset of heart failure.
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Vol 13 - N° 2
P. 212 - mai 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.