Superoxide dismutase mimetic nanozymes attenuate cardiac microvascular ischemia–reperfusion injury associated with hyperhomocysteinemia

Abstract

The combination of homocysteine (Hcy) and copper ion (Cu2+) induces cardiac microvascular ischemia–reperfusion injury (IRI) by causing oxidative stress in the reperfusion treatment of ischemic cardiopathy. Therefore, antioxidant elimination of reactive oxygen species (ROS) shows great potential in the treatment of IRI. Herein, cerium vanadate nanorods (CVNRs) were designed and developed as an efficient ROS scavenger for the treatment of myocardial IRI in hyperhomocysteinemic rat (HHcyR) model. Thanks to its outstanding superoxide dismutase (SOD)-like activity, the CVNRs showed a significant antioxidant effect in human cardiac microvascular endothelial cells treated with Hcy and Cu2+ under hypoxia/reperfusion condition and greatly preserved the morphology and function of mitochondria. Further intravenous administration of CVNRs significantly maintained the integrity and perfusion of microvasculature, minimized the microcirculation malfunction, and finally reduced the myocardial infarction and maintained the heart function after IRI. Moreover, the administration of CVNRs in HHcyR exhibited negligible organ toxicity and inflammation response, indicating their excellent biocompatibility and biosafety. Collectively, the SOD-mimicking CVNRs can serve as a promising antioxidant nanozyme to treat cardiac microvascular IRI complicated with hyperhomocysteinemia, providing a new prospect for the development of antioxidant nanozyme in IRI treatment even with other risk factors.