YAP/TAZ in vascular homeostasis and disease: context-dependent regulation and therapeutic opportunities

Abstract

Vascular homeostasis depends on coordinated responses among endothelial cells, vascular smooth muscle cells, and perivascular cells. The Hippo pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) integrate mechanical, metabolic, and biochemical cues within these cell types. Their effects are highly context-dependent, supporting vascular development and integrity under physiological conditions while promoting inflammation, maladaptive remodeling, or calcification in specific disease settings. This review synthesizes the regulatory networks that control YAP/TAZ across vascular cell types and examines their roles in atherosclerosis, angiogenesis, vascular calcification, and related disorders. We further assess emerging YAP/TAZ-directed therapies and define the central translational challenge: achieving cell-, site-, and stage-specific modulation without disrupting essential homeostatic and regenerative functions.