Endothelial Cell Phenotypic Plasticity in Cardiovascular Physiology and Disease: Mechanisms and Therapeutic Prospects

作者：Diego Barbosa de Queiroz, Juliana Montenegro Parente, Laena Pernomian, Emily Waigi, Mabruka Alfaidi, Wenbin Tan, Cameron G. McCarthy, Camilla F. Wenceslau · 发表于：American Journal of Hypertension · 年份：2025 · DOI：10.1093/ajh/hpaf027 · 被引用次数：9 · 研究领域：Single-cell and spatial transcriptomics

Endothelial cells (ECs) are a highly specialized and heterogeneous population that plays a fundamental role in maintaining vascular homeostasis, immune regulation, and blood flow control. Beyond serving as a physical barrier, ECs exhibit remarkable plasticity, undergoing phenotypic transitions, including endothelial-to-mesenchymal (EndMT), endothelial-to-hematopoietic (EndHT), endothelial-to-osteoblast (EndOT) and endothelial-to-immune-cell-like (EndICLT). These transitions allow ECs to adapt to developmental, physiological, and pathological conditions. Advances in single-cell RNA sequencing (scRNA-seq) and associated technologies have provided deeper insights into the molecular diversity of ECs across different vascular beds and stages of development, revealing their transcriptional heterogeneity and specialized functions. For example, ECs within the aortic arch display distinct phenotypic variations depending on their location, reflecting adaptations to regional differences in blood flow and shear stress. Activated EndMT has been implicated in the progression of various cardiovascular diseases, including hypertension, atherosclerosis, and vascular malformations by contributing to endothelial dysfunction, vascular wall inflammation, and remodeling. Recent therapeutic approaches aim to mitigate EndMT-associated vascular damage through interventions such as endothelial reprogramming, statins, and autophagy enhancers. Partial reprogramming of ECs has shown promise in restoring ...