Association of the PPARγ/PI3K/Akt pathway with the cardioprotective effects of tacrolimus in myocardial ischemic/reperfusion injury

Abstract

Myocardial ischemia/reperfusion injury (MIRI) induces severe arrhythmias and has a high risk of mortality. The aim of the present study was to investigate the effect of tacrolimus on arrhythmias, cardiac function, oxidative stress and myocardium apoptosis induced by MIRI, and to elucidate the underlying mechanism. The effects of MIRI and tacrolimus on arrhythmias, cardiac function parameters, myocardial oxidative stress and apoptosis were investigated in a rat model of MIRI. The phosphorylation of peroxisome proliferator‑activated receptor γ (PPARγ) and protein kinase B (Akt) was investigated via western blotting. After rats were treated with inhibitors of PPARγ/phosphoinositide 3‑kinase (PI3K)/Akt, cardiac function parameters were measured. The results demonstrated that the MIRI procedure induced arrhythmias and significant impairment of cardiac function, oxidative stress and apoptosis in cardiomyocytes (P<0.05). Tacrolimus significantly alleviated the arrhythmias and impairment of cardiac function and inhibited the oxidative stress and apoptosis in cardiomyocytes (P<0.05). The phosphorylation of PPARγ and Akt was significantly activated by tacrolimus, whereas inhibitors of PPARγ/PI3K/Akt significantly abolished the effects of tacrolimus (P<0.05). Together, these results suggest that tacrolimus may protect rats from MIRI through activation of the PPARγ/PI3K/Akt pathway.

Gastrodin prevents homocysteine‐induced human umbilical vein endothelial cells injury via PI3K/Akt/eNOS and Nrf2/ARE pathway

“…Nrf2 and eNOS are both modulated by the PI3K/Akt signalling pathway, the activation of which plays a pivotal role in cellular homeostasis under oxidative stress 27 . We have been suggested that Gas exerted its protective effects through a mechanism dependent on PI3K/Akt, which, based on our results above, indicated that Gas exerted its effect through the Cav‐1/eNOS and Nrf2/ARE pathways.…”

Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

“…For example, phosphatase PTEN that negatively regulates the PI3K/Akt pathway can be inhibited by ROS [234,235], exosomes derived from bone marrow stromal cells [236], or Achyranthes bidentata polypeptides [237], then enhancing Akt phosphorylation and promoting myocardial protection. Treatments targeting PI3K/Akt or related signaling pathways reduce reperfusion complications such as arrhythmias [238,239], myocardial stunning [239], myocardial no-reflow [240], and adverse remodeling [241]. [19,[91][92][93][94].…”

Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway

“…Experimental studies have indicated that intervention and ischemia preconditioning using some pharmacological agents can recruit the PI3K/Akt pathway and confer powerful cardioprotection [13]. It has been proposed that pharmacological targeting of the Akt pathway may potentially diminish ischemia reperfusion (IR) injury [14].…”