Circadian regulated control of myocardial ischemia-reperfusion injury

Trends Cardiovasc Med. 2022 Sep 20;S1050-1738(22)00120-7. doi: 10.1016/j.tcm.2022.09.003. Online ahead of print.


Circadian mechanisms have been associated with the pathogenesis of a variety of cardiovascular diseases, including myocardial ischemia-reperfusion injury (I-R). Myocardial ischemia resulting from impaired oxygen delivery to cardiac muscle sets into motion a cascade of cellular events that paradoxically triggers greater cardiac dysfunction upon reinstitution of coronary blood supply, a phenomenon known as I-R. I-R injury has been attributed to a number of cellular defects including increased reactive oxygen species (ROS), increased intracellular calcium and impaired mitochondrial bioenergetics that ultimately lead to cardiac cell death, ventricular remodeling and heart failure. Emerging evidence has identified a strong correlation between cellular defects that underlie I-R and the disrupted circadian. In fact, recent studies have shown that circadian dysfunction exacerbates cardiac injury following MI from impaired cellular quality control mechanisms such as autophagy, which are vital in the clearance of damaged cellular proteins and organelles such as mitochondria from the cell. The accumulation of cellular debris is posited as the central underlying cause of excessive cardiac cell death and ventricular dysfunction following MI. The complexities that govern the interplay between circadian biology and I-R injury following MI is at its infancy and understanding how circadian misalignment, such as in shift workers impacts I-R injury is of great scientific and clinical importance toward development of new therapeutic strategies using chronotherapy and circadian regulation to mitigate cardiac injury and improve cardiac outcomes after injury. In this review, we highlight recent advances in circadian biology and adaptive cellular quality control mechanisms that influence cardiac injury in response to MI injury with a specific focus on how circadian biology can be utilized to further cardiovascular medicine and patient care.

Keywords: Calcium overload; Cell death; Circadian; ER stress; Inflammation; Ischemia-reperfusion injury; Mitochondria; Myocardial infarction; Oxidative stress.

Publication types

  • Review