Insight into the Pathophysiology of Myocardial Infarction

Abstract

Myocardial infarction is classified as the irreversible myocardial cell death following ischemia. Ischemia could be initiated as a result of atherosclerotic or variable non-atherosclerotic causes. Consequent effects of ischemia are primarily caused due to oxidative stress which is the main precursor of cell death. Myocardial cell death is triggered through intrinsic or extrinsic pathways. In both pathways, apoptosis has been clearly explained through different studies but recently, necroptosis was determined to be involved. The heart has negligible ability for regeneration, thus infarcted regions are healed by replacing dead cells with scar formation. Infarct healing is triggered through an inflammatory cascade, induced by alarmins released from dying cells. Clearance of dead cells by immune cells is followed with the activation of fibroblasts to promote deposition of extracellular matrix proteins. This review discusses the events involved following ischemia including the mechanistic signalling during injury, inflammation, and repair of the infarcted heart. Moreover, the possible complications are mentioned along with the established treatment strategies and some new therapeutic approaches for myocardial infarction.

Cardiac Reverse Remodeling in Ischemic Heart Disease with Novel Therapies for Heart Failure with Reduced Ejection Fraction

“…Myocyte loss is a key factor in the development of ventricular remodeling in IHD. During ischemic conditions, cell death may be induced by activating an intrinsic pathway originating in the mitochondria and an extrinsic pathway mediated by several cell death receptors such as tumor necrosis factor (TNF) receptors [17]. As a result, processes such…”

“…Myocyte loss is a key factor in the development of ventricular remodeling in IHD. During ischemic conditions, cell death may be induced by activating an intrinsic pathway originating in the mitochondria and an extrinsic pathway mediated by several cell death receptors such as tumor necrosis factor (TNF) receptors [17]. As a result, processes such as apoptosis and necrosis are activated and lead to impaired contractility which will trigger the remodeling of the myocardium and ultimately progression to HF [18][19][20].…”

“…Similar to necrosis, it induces cell and organelle swelling with rupture of the plasma membrane [29][30][31][32]. This will cause an intense inflammatory reaction that exacerbates the damage in the infarcted myocardium [17,33]. Autophagy seems to play a significant yet controversial role in the pathogenesis of ventricular remodeling after MI.…”

“…In addition, aldosterone promotes fibrosis by directly stimulating fibroblast proliferation and enhancing collagen production [79][80][81]. All of these processes will alter the left ventricular configuration, from an initial elliptical to a spherical shape, and dilatation with increased end-systolic and end-diastolic volumes and reduced cardiac output [17].…”