1. Cardiac pericytes mediate the remodeling response to myocardial infarction
- Author
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Quijada, Pearl, Park, Shuin, Zhao, Peng, Kolluri, Kamal S.S., 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 T.D., Lowenstein, Charles J., Iruela-Arispe, M. Luisa, Carmichael, S. Thomas, Small, Eric M., and Ardehali, Reza
- Subjects
Heart attack -- Development and progression -- Complications and side effects ,Heart cells -- Health aspects -- Physiological aspects ,Cellular control mechanisms -- Health aspects -- Physiological aspects ,Muscle cells -- Health aspects -- Physiological aspects ,Health care industry - 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-[beta] signaling. Deleting TGF- [beta] 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., Introduction Injury to the adult mammalian heart results in irreversible loss of cardiomyocytes and triggers an inflammatory cascade that forms a collagen-rich scar. A significant component of fibrosis following myocardial [...]
- Published
- 2023
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