Cardiomyocyte death: mechanisms and translational implications

Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although treatments have improved, development of novel therapies for patients with CVD remains a major research goal. Apoptosis, necrosis, and autophagy occur in cardiac myocytes, and both gradual and acute cell death are hallmarks of cardiac pathology, including heart failure, myocardial infarction, and ischemia/reperfusion. Pharmacological and genetic inhibition of autophagy, apoptosis, or necrosis diminishes infarct size and improves cardiac function in these disorders. Here, we review recent progress in the fields of autophagy, apoptosis, and necrosis. In addition, we highlight the involvement of these mechanisms in cardiac pathology and discuss potential translational implications.

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

“…Apoptosis is an immunoquiescent form of cell death that requires the activity of cysteine proteases known as caspases (42). It has been shown that mice lacking the death receptor FAS or mice treated with chemical inhibitors of caspases experience reduced heart infarct sizes and less apoptotic positive cells after ischemic and reperfusion injuries (43).…”

The role of mitochondria in cardiac development and protection

“…ARE promoters control antioxidant genes such as SOD2, heme oxygenases and the nuclear respiratory factor-1 activates the mitochondrial calcium uniporter and in the absence of functional OXPHOS efficiently dissipates the mitochondrial membrane potential, on which the porter is dependent [32]. When sustained, Ca 2+ stress will trigger necrotic cell death [33]. If O2 levels suddenly increase, as it happens in reperfusion after ischemia, the mitochondrial membrane potential is restored, triggering intake of additional Ca 2+ , opening of the mitochondrial permeability transition pore (MPTP) and resulting in cell death.…”

“…For example, the release of cytochrome c, a hallmark of intrinsic apoptotic pathway, is not sufficient to induce apoptosis in isolated cardiomyocytes [41,42]. Instead, cardiomyocytes seem to focus on damage tolerance and repair [33]. As ROS can activate both survival and death signaling, depending on the intensity of the damage [33], cardiomyocyte damage tolerance should be closely linked to the mitochondrial function.…”

“…Instead, cardiomyocytes seem to focus on damage tolerance and repair [33]. As ROS can activate both survival and death signaling, depending on the intensity of the damage [33], cardiomyocyte damage tolerance should be closely linked to the mitochondrial function. The key mechanism to contain cellular damage and adapt to oxidative stress is to target damaged organelles and cellular macromolecules to degradation in a process called autophagy.…”

Mitochondrial disruption occurs downstream from β-adrenergic overactivation by isoproterenol in differentiated, but not undifferentiated H9c2 cardiomyoblasts: Differential activation of stress and survival pathways

“…Once mitochondrial function is affected, critical ATP-dependent mechanisms are compromised and mitochondriainduced apoptotic cell death is activated (Chiong et al, 2011). Increased mitochondrial production of ROS play an important role in the regulation of multiple stress and toxicity responses (Afanas'ev, 2011).…”