Nrf2 Deficiency Aggravates PM-induced Cardiomyopathy by Enhancing Oxidative Stress, Fibrosis and Inflammation Via RIPK3-regulated Mitochondrial Disorder

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Mar 18

PMID 32182211

Citations 16

Authors

Chenxu Ge

Linfeng Hu

Deshuai Lou

Qiang Li

Jing Feng

Yekuan Wu

Jun Tan

Minxuan Xu

Affiliations

Soon will be listed here.

Abstract

PM is a well-known air pollutant threatening public health, and long-term exposure to PM increases the risk of cardiovascular diseases. Nrf2 plays a pivotal role in the amelioration of PM-induced lung injury. However, if Nrf2 is involved in PM-induced heart injury, and the underlying molecular mechanisms have not been explored. In this study, wild type (Nrf2) and Nrf2 knockout (Nrf2) mice were exposed to PM for 6 months. After PM exposure, Nrf2 mice developed severe physiological changes, lung injury and cardiac dysfunction. In the PM-exposed hearts, Nrf2 deficiency caused significant collagen accumulation through promoting the expression of fibrosis-associated signals. Additionally, Nrf2 mice exhibited greater oxidative stress in cardiac tissues after PM exposure. Furthermore, PM-induced inflammation in heart samples were accelerated in Nrf2 mice through promoting inhibitor of α/nuclear factor κB (IκBα/NF-κB) signaling pathways. We also found that Nrf2 aggravated autophagy initiation and glucose metabolism disorder in hearts of mice with PM challenge. Cardiac receptor-interacting protein kinase 3 (RIPK3) expression triggered by PM was further enhanced in mice with the loss of Nrf2. Collectively, these results suggested that strategies for enhancing Nrf2 could be used to treat PM-induced cardiovascular diseases.

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