Cardiac pericytes mediate the remodeling response to myocardial infarction

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.

Automated summary

The role of pericytes in ischemia-induced remodeling in the heart was investigated. Pericytes migrated to the injury site and expressed profibrotic genes, leading to increased vessel leakage after myocardial infarction. Single-cell RNA-Seq analysis revealed the induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-beta signaling. Targeting TGF-beta receptor 1 in pericytes reduced fibrosis and improved cardiac function after MI, while genetic ablation of pericytes resulted in excessive vascular permeability, declined cardiac function, and increased mortality. These findings highlight the importance of pericytes in controlling vascular homeostasis and the fibrotic response to acute ischemic injury, providing insights for novel therapeutic approaches.