Myocardial Infarction: Perspectives on Cardiac Regeneration and Cardiac Remote Conditioning Interventions to Limit Cellular Injury

Abstract

Acute myocardial infarction initiates a cascade of events including loss of protein homeostasis and chronic inflammation that affect overall cellular repair and senescence. This contributes to loss of cardiomyocytes and consequent formation of fibrotic scar. In certain vertebrate species, the heart can completely self-repair or regenerate after myocardial injury; however, this does not appear to be the case for humans. Despite this limitation, studies using novel non-pharmacologic interventions designed to protect against ischemic damage and to improve patient outcomes are ongoing. Remote ischemic conditioning stratagems are used to attenuate ischemia-reperfusion injury in clinical and animal studies; endogenous protective factors that stimulate complex signal transduction pathways are deemed responsible. Some of these factors could conceivably act in concert with those involved in regulating cardiovascular regeneration. Numerous studies have focused on cardiac regenerative interventions using stem-cell based therapies and transplantation of cardiomyocyte (or other cell types) or biocompatible matrices. This review discusses recent progress of pre-clinical and clinical translational studies for cardiac regeneration. In addition, we submit that interventions using cellular adjunctive therapies combined with remote ischemic conditioning may prove to be of interest in the battle to find novel strategies for protection against cardiac injury. are described in the scientific literature; myocardial stunning, i.e. viable cardiomyocytes that exhibit prolonged post-ischemic contractile dysfunction even after reperfusion, and myocardial hibernation, i.e. viable, but chronically contractile dysfunctional cardiomyocytes. While the pathogenesis of cell death in non-cardiac cells is less considered in most studies, it is clear that vascular endothelial and smooth muscle cells along with nervous system components within the ischemic zone are negatively affected by coronary occlusion; this contributes significantly to overall loss of cardiac contractile function and limits recovery potential. Loss of these myocardial components probably renders the affected tissue non-salvageable for a number of reasons including no-reflow, or disrupted electrical conduction, etc. Timely reperfusion of the infarct-related artery by various clinical strategies (just enumerate them as reperfusion therapy which may be pharmacological, primary percutaneous coronary intervention, primary PCI, urgent coronary artery bypass graft, appears to limit overall myocardial damage; however, reperfusion itself may exacerbate injury via apoptosis or autophagy [19]. While patient survival after ischemia has markedly improved over the last forty years, the prevalence of chronic heart failure due, in part, to remodeling of the damaged left ventricle has also increased [20] [21]. Cardiac repair is a complex, tightly regulated process between innate and immune systems [22] that includes inflammation and infiltration of the infarct area by immune cell subtypes (neutro...

Acute Myocardial Infarction: Perspectives on Physiopathology of Myocardial Injury and Protective Interventions

“…to repair damaged myocardium is another promising intervention to restore post-ischemic cardiac dysfunction (cf. recent review from Kingma [106]). Basic studies designed to better understand underlying mechanisms are ongoing; however, many limitations (i.e.…”

The Cellular Stress Response Interactome and Extracellular Matrix Cross-Talk during Fibrosis: A Stressed Extra-Matrix Affair

“…Fibroblasts are key players in the secretion, deposition, organization and regulation of ECM turnover, however, their phenotypic heterogeneity, functional diversity, and attendant signalling pathways that modulate fibrotic over regenerative repair in cardiac diseases remain largely indecisive [25][26][27][28][29][30][31][32][33][34][35][36][37] involving lung, liver, and heart [29], and improved understanding of its cross-talk with fibroblasts is in progress as the attendant pathways are still controversial. Therefore, improved understanding of the molecular mechanisms and cross-talk underlying fibroblast activation and cardiomyocyte death are central for restoring cardiac homeostasis, designing novel regenerative approaches and developing anti-fibrotic therapies.…”