1. Cardiac pericytes mediate the remodeling response to myocardial infarction
- Author
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Quijada, Pearl, Park, Shuin, Zhao, Peng, Kolluri, Kamal SS, Wong, David, Shih, Kevin D, Fang, Kai, Pezhouman, Arash, Wang, Lingjun, Daraei, Ali, Tran, Matthew D, Rathbun, Elle M, Villar, Kimberly N Burgos, Garcia-Hernandez, Maria L, Pham, Thanh TD, Lowenstein, Charles J, Iruela-Arispe, M Luisa, Carmichael, S Thomas, Small, Eric M, and Ardehali, Reza
- Subjects
Medical Physiology ,Biomedical and Clinical Sciences ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Heart Disease ,Genetics ,Aetiology ,1.1 Normal biological development and functioning ,Underpinning research ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Mice ,Animals ,Pericytes ,Myocardial Infarction ,Heart ,Fibrosis ,Extracellular Matrix ,Ventricular Remodeling ,Myocardium ,Cardiology ,Cardiovascular disease ,Vascular Biology ,Medical and Health Sciences ,Immunology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac ejection fraction. Furthermore, genetic ablation of Cspg4-expressing cells resulted in excessive vascular permeability, a decline in cardiac function, and increased mortality in the second week after MI. These data reveal an essential role for cardiac pericytes in the control of vascular homeostasis and the fibrotic response after acute ischemic injury, information that will help guide the development of novel strategies to preserve vascular integrity and attenuate pathological cardiac remodeling.
- Published
- 2023