Protective role of TAT-HSP70 after myocardial I/R injury

Martin A. Meenakshi; Erik G. Seth; Michael Robbie

Abstract

Myocardial ischemia-reperfusion (I/R) injury remains one of the greatest unresolved therapeutic challenges in cardiovascular medicine. Several strategies that target various apoptosis pathways to limit myocardial infarct size have been researched, but none have been translated into effective therapy yet. Emerging evidence indicates that heparan sulfate proteoglycan expression in mitochondria of the infarcted heart and that inhibition of HSP70 expression increases mitochondrial ROS production and subsequent apoptosis. In this article, explain the cardioprotective mechanism of HSPs is reviewed, and the overexpression of HSPs in myocardial tissue of TAT-HSP70 transgenic mice showed myocardial protective effect on related research in myocardial ischemia. The protective effect of TAT-HSP70 in multiple organs for I/R injury is reviewed. In addition, atrial and endothelial phenotype changes in TAT-HSP70 prevent the development of pulmonary arterial hypertension (PH) and improve cardiopulmonary function in PH rat models. Intraperitoneal TAT-HSP70 exerted a direct cardioprotective effect in myocardial infarction in well-established mice and demonstrated that TAT-HSP70 is resistant to ischemia, increased energy production, and increased AMPK activity. TAT-HSP70 injection for 24 h also inhibited neutrophil infiltration of infarcts. Administering TAT-HSP70 (magnetic nanoparticle) conjugate 10 min before reperfusion increased efficacy, prevented local ischemic endothelial injury in patients with myocardial infarction, and reduced the incidence of reperfusion injury-related complications compared to placebo. In summary, the protective effect of TAT-HSP70 in myocardial I/R injury plays a role in subsequent studies and clinical applications.

Keywords: TAT-HSP70; Myocardial I/R injury; Heat shock response

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