Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction.

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Frontiers in Pharmacology Pub Date : 2025-01-10 eCollection Date: 2024-01-01 DOI:10.3389/fphar.2024.1503757
Wenjing Liao, Jinduan Lin, Wenli Wang, Ming Zhang, Yanfang Chen, Xin Li, Huan Liu, Pan Xia Wang, Guojun Zhao, Jijun Fu, Xiaoqian Wu
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引用次数: 0

Abstract

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and mitigating oxidative stress is crucial in managing MI. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in combating oxidative stress and facilitating cardiac remodeling post-MI. Here, we engineered Cerium oxide (CeO2) nanoparticle-guided assemblies of ceria/Nrf2 nanocomposites to deliver Nrf2 plasmids. The CeO2/Nrf2 nanocomposites effectively activated the Nrf2/antioxidant response element (ARE) signaling pathway both in vivo and in vitro. In a mouse MI model induced by permanent ligation of the left anterior descending artery (LAD), CeO2/Nrf2 nanocomposites were administered via tail vein injection, predominantly targeting circulating monocytes and macrophages which will be recruited to the heart post MI due to the acute inflammatory response. We demonstrated that CeO2/Nrf2 nanocomposites alleviated cardiac systolic dysfunction and significantly reduced infarct size and scar fibrosis post-MI. Furthermore, CeO2/Nrf2 nanocomposites effectively mitigated MI-induced oxidative stress and downregulated Nrf2-regulated inflammatory genes (tumor necrosis factor-α, IL-6, and inducible nitric oxide synthase), thereby reducing cardiomyocyte apoptosis. These findings indicate that CeO2/Nrf2 nanocomposites significantly enhance Nrf2 signaling activation and confer protection against MI. This study identifies CeO2/Nrf2 nanocomposites as a promising strategy for post-MI therapy.

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来源期刊
Frontiers in Pharmacology
Frontiers in Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.80
自引率
8.90%
发文量
5163
审稿时长
14 weeks
期刊介绍: Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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