Significance: The vascular extracellular matrix (ECM) not only provides mechanical stability but also manipulates vascular cell behaviors, which are crucial for vascular function and homeostasis. ECM remodeling, which alters vascular wall mechanical properties and exposes vascular cells to bioactive molecules, is involved in the development and progression of hypertension. Recent Advances: This brief review summarized the dynamic changes in ECM components and their modification and degradation during hypertension and after antihypertensive treatment. We also discussed how alterations in the ECM amount, assembly, mechanical properties, and degradation fragment generation provide input into the pathological process of hypertension. Critical Issues: Although the relevance between ECM remodeling and hypertension has been recognized, the underlying mechanism by which ECM remodeling initiates the development of hypertension remains unclear. Therefore, the modulation of ECM remodeling on arterial stiffness and hypertension in genetically modified rodent models is summarized in this review. The circulating biomarkers based on ECM metabolism and therapeutic strategies targeting ECM disorders in hypertension are also introduced. Future Directions: Further research will provide more comprehensive understanding of ECM remodeling in hypertension by the application of matridomic and degradomic approaches. The better understanding of mechanisms underlying vascular ECM remodeling may provide novel potential therapeutic strategies for preventing and treating hypertension. Antioxid. Redox Signal. 34, 765-783.
Keywords: extracellular matrix; hypertension; remodeling; stiffness; vascular smooth muscle cell.