The role of pericytes in homeostasis and cardiovascular disease: A comprehensive review.

backgroundPericytes, as critical mural cells of the vascular wall, play multifaceted and context-dependent roles in maintaining vascular integrity, regulating microcirculatory homeostasis, and mediating interactions between the vasculature and surrounding tissues. Beyond their canonical functions in vascular stabilization and angiogenesis, recent preclinical and clinical studies have increasingly implicated pericyte dysfunction in the pathogenesis of various cardiovascular diseases (CVDs), including atherosclerosis, myocardial ischemia-reperfusion (I/R) injury, pulmonary arterial hypertension (PAH), and ischemic stroke. AIM OF REVIEW: This review aims to comprehensively collate and analyze recent progress in understanding pericyte biology in major CVDs. Specifically, it determines the core roles of pericytes in atherosclerosis based on mediating plaque neovascularization, promoting plaque instability via detachment or pro-inflammatory activation, myocardial I/R injury based on regulating microvascular permeability, participating in post-infarction fibrosis and vascular repair), PAH based on abnormal proliferation and differentiation leading to pulmonary vascular remodeling, and ischemic stroke based on maintaining blood-brain barrier integrity, modulating neurovascular unit repair. KEY SCIENTIFIC CONCEPTS OF REVIEW: By integrating evidence from preclinical models such as lineage-tracing mice, disease-specific animal models and clinical samples, this review elucidates the common and disease-specific mechanisms linking pericyte dysfunction to CVD pathogenesis, and highlights the therapeutic promise of targeting pericyte biology. Key scientific concepts explored include the interplay between pericyte phenotypic plasticity and microenvironmental cues, the role of pericyte-endothelial cell crosstalk in vascular homeostasis and dysfunction, and the clinical relevance of pericyte subpopulation heterogeneity. Ultimately, this work provides novel mechanistic insights into CVD progression and offers a framework for advancing pericyte-directed therapeutic development, bridging the gap between basic research and clinical application to improve outcomes for patients with cardiovascular disorders.