Inhibition of miR-153 ameliorates ischemia/reperfusion-induced cardiomyocytes apoptosis by regulating Nrf2/HO-1 signaling in rats

Abstract

Background Previous in vitro studies demonstrated that suppression of microRNAs might protect cardiomyocytes and neurons against oxygen–glucose deprivation and reoxygenation (OGD/R)-induced cell apoptosis. However, whether the protective effect of miR-153-inhibition on cardiomyocytes can be observed in the animal model is unknown. We aimed to address this question using a rat model of ischemia–reperfusion (I/R). Methods Rats were received the intramyocardial injection of saline or adenovirus-carrying target or control gene, and the rats were subjected to ischemia/reperfusion (I/R) treatment. The effects of miR-153 on I/R-induced inflammatory response and oxidative stress in the rat model were assessed using various assays. Results We found that suppression of miR-153 decreased cleaved caspase-3 and Bcl-2-associated X (Bax) expression, and increased B cell lymphoma 2 (Bcl-2) expression. We further confirmed that Nuclear transcription factor erythroid 2-like 2 (Nrf2) is a functional target of miR-153, and Nrf2/Heme oxygenase-1 (HO-1) signaling was involved in miR-153-regulated I/R-induced cardiomyocytes apoptosis. Inhibition of miR-153 reduced I/R-induced inflammatory response and oxidative stress in rat myocardium. Conclusion Suppression of miR-153 exerts a cardioprotective effect against I/R-induced injury through the regulation of Nrf2/HO-1 signaling, suggesting that targeting miR-153, Nrf2, or both may serve as promising therapeutic targets for the alleviation of I/R-induced injury.

miR-3587 Targets HMOX1 to Attenuate Ferroptotic Renal Injury Following Ischemia-Reperfusion

“…However, HMOX1 can also promote ferroptosis in cancer cells in therapeutic contexts [22]. There is also prior evidence that HMOX1 primarily plays a bene cial role in IR injury [23]. Pei et al demonstrated that normobaric hyperoxia can promote HMOX1 upregulation, thereby protecting against renal IR injury [23].…”

The Antioxidant Transcription Factor Nrf2 in Cardiac Ischemia–Reperfusion Injury

“…In this latter study, attenuating ROS overproduction in reoxygenation with the antioxidant N-acetyl cysteine (NAC) suppressed Nrf2 activation, pointing to ROS as signaling mediators of Nrf2. Along the same line, activation of the Nrf2 pathway by miRNAs protects rat and mouse cardiomyocytes against in vitro IR or oxygen and glucose deprivation (OGD) followed by reperfusion [ 114 , 115 , 116 ]. We have shown that Nrf2 expression is elevated during reperfusion in isolated perfused mouse hearts (Langendorff system) [ 117 ].…”

“…Several miRNAs modulate IR injury by regulating the Nrf2 pathway (reviewed in [ 122 , 123 , 124 ]). Thus, upregulation of miRNA-153 inhibits Nrf2/heme oxygenase-1 and induces ROS production and apoptosis in cardiomyocytes after OGD followed by reoxygenation [ 115 ] and in a rat model of IR [ 116 ]. Overexpression of miR-210 in cardiomyocytes reduces ROS production and cell death, while downregulation of miR-210 increases ROS levels after hypoxia/reoxygenation [ 125 ].…”

Role of Nrf2 and Its Activators in Cardiocerebral Vascular Disease

“…For example, the inhibition of miR-148b-3p protected neurons against OGD/R-induced apoptosis and ROS production by enhancing Sestrin2/Nrf2 antioxidant signaling [ 177 ]. Inhibition of miR-153 ameliorated ischemia reperfusion-induced cardiomyocyte apoptosis by regulating the Nrf2/HO-1 signaling pathway in rats [ 178 ]. Interestingly, dietary compounds have the potential to control atherosclerosis by targeting miR-155 to activate the Nrf2 pathway [ 179 ].…”