超氧化物歧化酶
再灌注损伤
心室重构
药理学
医学
缺血
不利影响
心脏病学
氧化应激
心肌缺血
内科学
心力衰竭
作者
Peter J. Altshuler,Alexis R. Schiazza,Lijun Luo,Mark R. Helmers,Bonirath Chhay,Jason J. Han,Robin Hu,D. Alan Herbst,Andrew Tsourkas,Zhiliang Cheng,Pavan Atluri
标识
DOI:10.1002/adtp.202100036
摘要
Abstract Early revascularization is critical to reduce morbidity after myocardial infarction, although reperfusion incites additional oxidative injury. Superoxide dismutase (SOD) is an antioxidant that scavenges reactive oxygen species (ROS) but has low endogenous expression and rapid myocardial washout when administered exogenously. This study utilizes a novel nanoparticle carrier to improve exogeneous SOD retention while preserving enzyme function. Its role is assessed in preserving cardiac function after myocardial ischemia‐reperfusion (I/R) injury. Here, nanoparticle‐encapsulated SOD (NP‐SOD) exhibits similar enzyme activity as free SOD, measured by ferricytochrome‐c assay. In an in vitro I/R model, free and NP‐SOD reduce active ROS, preserve mitochondrial integrity, and improve cell viability compared to controls. In a rat in vivo I/R injury model, NP‐encapsulation of fluorescent‐tagged SOD improves intramyocardial retention after direct injection. Intramyocardial NP‐SOD administration in vivo improves left ventricular contractility at 3‐h post‐reperfusion by echocardiography and 4‐weeks by echocardiography and invasive pressure–volume catheter analysis. These findings suggest that NP‐SOD mitigates ROS damage in cardiac I/R injury in vitro and maximizes retention in vivo. NP‐SOD further attenuates acute injury and protects against myocyte loss and chronic adverse ventricular remodeling, demonstrating potential for translating NP‐SOD as a therapy to mitigate myocardial I/R injury.
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