Tumor Necrosis Factor Family Members and Myocardial Ischemia-Reperfusion Injury: State of the Art and Therapeutic Implications

Ischemic heart disease is the principal cause of death worldwide and clinically manifests as myocardial infarction (MI), stable angina, and ischemic cardiomyopathy. Myocardial infarction is defined as an irreversible injury due to severe and prolonged myocardial ischemia inducing myocardial cell death. Revascularization is helpful in reducing loss of contractile myocardium and improving clinical outcome. Reperfusion rescues myocardium from cell death but also induces an additional injury called ischemia-reperfusion injury. Multiple mechanisms are involved in ischemia-reperfusion injury, such as oxidative stress, intracellular calcium overload, apoptosis, necroptosis, pyroptosis, and inflammation. Various members of the tumor necrosis factor family play a key role in myocardial ischemia-reperfusion injury. In this article, the role of TNF alpha, CD95L/CD95, TRAIL, and the RANK/RANKL/OPG axis in the regulation of myocardial tissue damage is reviewed together with their potential use as a therapeutic target.

Automated summary

Ischemic heart disease, including myocardial infarction, stable angina, and ischemic cardiomyopathy, is a leading cause of death worldwide. Revascularization can reduce myocardial loss and improve clinical outcomes, but it also carries the risk of ischemia-reperfusion injury. This article reviews the role of tumor necrosis factor family members, such as TNF-alpha, CD95L/CD95, TRAIL, and the RANK/RANKL/OPG axis, in myocardial tissue damage and their potential as therapeutic targets.