Apelin13 Loaded Nano-Niosomes Confer Cardioprotection in a Rat Model of Myocardial Ischemia Reperfusion by Targeting the Nrf2/HO-1 Pathway.

Although apelin-13 has cardioprotective impact, its short half-life in the bloodstream has challenged its clinical application. Using nanocarriers can increase the bioavailability, functionality, and stability of drugs. Current investigation aims to find whether apelin13-loaded nano-niosomes confer cardioprotection in an animal model of myocardial ischemia/reperfusion injury (MI/R) via suppressing ferroptosis, targeting Nrf2 pathway, and AMPK/GSK-3β axis. Ligation of the left anterior coronary artery descending was done to establish the MI/R model and 15 μg/kg of apelin13-loaded nano-niosomes were intramyocardially administrated. Echocardiography, RT-PCR, immunohistochemistry, western blot, ELISA kits, and H&E staining were applied to measure the related indicators. Treatment with both apelin13 and apelin13 loaded nano-niosomes could improve cardiac function and attenuate oxidative stress, myocardial inflammatory factors, and hence ferroptosis by activating the Nrf2 and its downstream proteins HO1, NQO1, AMPK/GSK-3β signaling pathway. In conclusion, apelin13-loaded nano-niosomes are effective MI therapeutic agents against MI/R-induced ferroptosis by activation of Nrf2 via AMPK/GSK-3β axis.