Partial Mural Cell Ablation Disrupts Coronary Vasculature Integrity and Induces Systolic Dysfunction
Lauriane Cornuault1, François-Xavier Hérion1, Célia Bourguignon1
1University of Bordeaux, Inserm, Biology of Cardiovascular Diseases Pessac France.
Insights
Cardiac pericyte depletion significantly impairs heart function, causing both systolic and diastolic dysfunction. This highlights the crucial role of pericytes in maintaining cardiac health and suggests their dysfunction contributes to heart disease.
Area of Science:
- Cardiovascular Biology
- Cell Biology
- Vascular Biology
Background:
- Pericytes are vital for vascular integrity in the brain and retina.
- Their role in the heart remains largely unexplored.
Purpose of the Study:
- To investigate the structural and functional consequences of partial pericyte depletion in adult mouse hearts.
Main Methods:
- Utilized platelet-derived growth factor receptor β-Cre/ERT2; RosaDTA mice for pericyte depletion.
- Assessed cardiac function using echocardiography and left ventricular catheterization.
- Analyzed tissue-level changes including endothelium leakage, immune cell infiltration, and gene expression.
Main Results:
- Pericyte-depleted mice exhibited reduced ejection fraction and increased end-diastolic pressure (systolic and diastolic dysfunction).
- Demonstrated decreased contractility and impaired relaxation (dP/dtmin).
- Observed increased coronary endothelium leakage, CD45+ cell infiltration, and altered expression of key cardiac proteins (e.g., connexin 43).
Conclusions:
- Cardiac pericyte depletion leads to significant systolic and diastolic dysfunction.
- Pericyte dysfunction is implicated as a potential contributor to cardiac diseases.
- Cardiac pericytes undergo remodeling in response to injury.
Abstract:
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; RosaDTA mice and compared their phenotype with that of control mice (RosaDTA) 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/dtmin). 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.
