Circadian regulation of vascular function: Metabolism as a link from molecular mechanisms to clinical implications

Abstract

Circadian rhythms act as central coordinators of vascular physiology, synchronizing metabolic and hemodynamic processes across different vascular beds. Cell-autonomous clocks dynamically regulate vascular functions, including vasodilation and inflammatory responses, in endothelial cells, smooth muscle cells, and fibroblasts. Emerging evidence indicates extensive crosstalk with metabolic cell death pathways, particularly lipophagy-mediated lipid turnover, redox stress-triggered disulfidptosis, and glucotoxicity-induced metabolic collapse, all of which display circadian rhythmicity. Disruption of these pathways, such as in shift workers or individuals carrying clock gene mutation, significantly increases the risk of hypertension, atherosclerosis, and microvascular dysfunction. In this review, we highlight translational strategies that leverage circadian biology, including chronotherapy, pharmacological modulation of core circadian clock components, light-dark synchronization, and lifestyle interventions. We also emphasize that future research should aim to decode the spatiotemporal regulation of circadian-metabolic networks, which may offer novel insights for precision medicine approaches targeting vascular metabolic disorders.