Circadian mechanisms in heart failure: Cell-specific regulation and chrono-medicine

Emerging evidence indicates that circadian rhythms profoundly influence the pathophysiology of heart failure (HF). The circadian clock system governs myocardial functions via synchronized actions from multiple cell types involving cardiomyocytes and non-cardiomyocytes. This review summarizes state-of-the-art advances on the cardiovascular circadian system and provides a perspective on time-of-day effects in the pathophysiology of HF, including energy metabolism, tissue inflammation and fibrosis. In particular, we focus on cell-specific circadian regulation and synthesize how circadian clocks across cardiomyocytes, vascular cells, fibroblasts, and adipocytes interact to regulate the pathophysiology of HF. Based on this framework, we discuss how synchronizing internal and external time cues via clock-modulating compounds and/or time-restricted eating (TRE) may prevent HF or facilitate rehabilitation. Together, this Review provides a timely synthesis of current understanding of HF as a function of biological timing and highlights potential chronotherapeutic strategies.