Autophagy as a novel therapeutic target in vascular calcification

Abstract

The autophagy pathway is a key regulator of cellular metabolism and homeostasis, and plays a critical role in maintaining normal vascular cell function. It is well recognised that autophagy can regulate endothelial cell homeostasis, vascular smooth muscle cell (VSMC) phenotype transition, and calcium (Ca²⁺) homeostasis in VSMCs. Emerging evidence has demonstrated that autophagy directly protects against vascular calcification (VC). Crosstalk between endosomes, dysfunctional mitochondria, autophagic vesicles and Ca²⁺ and phosphate (Pi) enriched matrix vesicles (MVs) may underpin the pathogenesis of VC. In this review, we summarize the current experimental evidence in understanding how autophagy maintains normal vascular cell function and its protective role against vascular calcification. We also discuss the underlying molecular and cellular mechanisms through which autophagy inhibits vascular calcification. Pharmacological modulation of autophagy may offer an exciting new strategy for the treatment of vascular calcification.

Keywords: Autophagy; Matrix vesicles; Phenotype transition; Vascular calcification; Vascular cell function.