Signaling Pathways in Cardiac Myocyte Apoptosis

Abstract

Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation.

The Long Non-Coding RNA SNHG1 Attenuates Cell Apoptosis by Regulating miR-195 and BCL2-Like Protein 2 in Human Cardiomyocytes

“…Ischemic heart disease is a big threat to the human heath worldwide, and studies have demonstrated that dysregulation of cardiomyocyte apoptosis contributed to the development of ischemia heart disease such as heart failure and myocardial infarction [7]. To understand the molecular mechanisms that regulate cardiomyocyte apoptosis is important treatment is a potent inducer for cardiomyocyte apoptosis, which has been welldocumented in many studies [22].…”

“…Ischemia/reperfusion-induced cell injury is complex and involves a variety of signaling pathways. Recent studies have shown that apoptosis plays a key role in the cardiac damage caused by ischemia/reperfusion [6,7]. Unfortunately, the molecular mechanism involved in regulating apoptosis of cardiomyocytes remains unclear.…”

Caspase-Independent Pathway is Related to Nilotinib Cytotoxicity in Cultured Cardiomyocytes

“…1C). Although caspase is a major cellular apoptosis pathway in a numerous types of cells [11], other signaling pathway may also be involved in nilotinib-induced H9C2 injury [13]. In cultured H9C2 and primary cardiomyocytes, we inhibited nilotinib-induced caspase3 activation by using 50 µM of z-VAD-fmk, a pan caspase inhibitor (Fig.…”

Acute Myocardial Injury: A Perspective on Lethal Reperfusion Injury

“…apoptosis, autophagy, oncosis) also merit attention. Conditions that control the transition from one status to the other have been widely debated [14,15]. Recently, Jennings suggested, "myocytes are irreversibly injured when they fail to survive after restoration of the environment to normal" [3].…”

“…Though essential during cardiac development, apoptosis is associated with ischemic heart disease, reperfusion injury, cardiomyopathy and heart failure [75]; the contribution of apoptosis to reperfusion injury remains the subject of ongoing debate [76,77]. Intracellular signalling pathways, along with morphologic, biochemical and molecular pathways responsible for regulation of apoptosis in cardiocytes have recently been discussed [14,15,78]. Ohno and coworkers postulated that myocyte damage during ischemia-reperfusion progressed from a reversible oncosis state to irreversible oncosis with or without DNA fragmentation [79].…”