Abstract
Despite the increasing success of interventional coronary reperfusion strategies, mortality related to acute myocardial infarction (MI) is still substantial. MI is defined as sudden death of myocardial tissue caused by an ischemic episode. Ischaemia leads to adverse remodelling in the affected myocardium, inducing metabolic and ionic perturbations at a single cell level, ultimately leading to cell death. The adult mammalian heart has limited regenerative capacity to replace lost cells. Identifying and enhancing physiological cardioprotective processes may be a promising therapy for patients with MI. Studies report an increasing amount of evidence stating the intricacy of the pathophysiology of the infarcted heart. Besides apoptosis, other cellular phenotypes have emerged as key players in the ischemic myocardium, in particular senescence, inflammation, and dedifferentiation. Furthermore, some cardiomyocytes in the infarct border zone uncouple from the surviving myocardium and dedifferentiate, while other cells become senescent in response to injury and start to produce a pro-inflammatory secretome. Enhancing electric coupling between cardiomyocytes in the border zone, eliminating senescent cells with senolytic compounds, and upregulating cardioprotective cellular processes like autophagy, may increase the number of functional cardiomyocytes and therefore enhance cardiac contractility. This review describes the different cellular phenotypes and pathways implicated in injury, remodelling, and regeneration of the myocardium after MI. Moreover, we discuss implications of the complex pathophysiological attributes of the infarcted heart in designing new therapeutic strategies.
Highlights
Myocardial infarction (MI) is defined as the myocardial injury that involves cell loss due to prolonged ischaemia [1]
Despite the increasingly improved logistics of ischaemic pre- or post-conditioning, reperfusion still exacerbates the adverse changes induced by myocardial ischaemia and leading to infarction, such as rupture of mitochondria, even higher ROS levels than during ischaemia, disruption of sarcolemmal organization, and increased inflammation [3]
Knockout of Heme oxygenase (HO)-1 exacerbates ischemia/reperfusion-induced myocardial injury [60, 61]. These studies suggest that HO-1 is involved in cardioprotection post-myocardial infarction (MI) through inhibition of CMs senescence and that enhancing HO-1 expression could improve heart function after injury
Summary
Myocardial infarction (MI) is defined as the myocardial injury that involves cell loss due to prolonged ischaemia [1]. After experimentally induced MI, ischemic injury initiates cell autophagy, apoptosis and immune-inflammatory reactions for clearance of damaged organelles and cells due to DNA damage, oxidative stress and mitochondrial dysfunction, leading to senescence in CMs. These CMs that become senescent after MI activate p16 and p53, upregulate enzyme activity of SA-β-gal and secretion of SASP, including the proinflammatory factors IL-1, IL-6 and TNF-α [54], suggesting that accumulation of senescent cells is a reason for organ aging, but plays a role in the progress of myocardial damage after ischemic injury and contributes to the decrease of heart function.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
