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Superoxide Dismutase‐Loaded Nanoparticles Attenuate Myocardial Ischemia‐Reperfusion Injury and Protect against Chronic Adverse Ventricular Remodeling
Author(s) -
Altshuler Peter J.,
Schiazza Alexis R.,
Luo Lijun,
Helmers Mark R.,
Chhay Bonirath,
Han Jason J.,
Hu Robin,
Herbst David Alan,
Tsourkas Andrew,
Cheng Zhiliang,
Atluri Pavan
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202100036
Subject(s) - superoxide dismutase , reperfusion injury , ventricular remodeling , ischemia , medicine , cardiology , adverse effect , myocardial ischemia , pharmacology , oxidative stress , heart failure
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.