Regulation of Nrf2 Signaling Pathway in Heart Failure: Role of Extracellular Vesicles and Non-coding RNAs

Overview

Journal Free Radic Biol Med

Specialties Biochemistry
Biology
General Medicine

Date 2021 Mar 20

PMID 33741451

Citations 28

Authors

Changhai Tian

Lie Gao

Irving H Zucker

Affiliations

Soon will be listed here.

Abstract

The balance between pro- and antioxidant molecules has been established as an important driving force in the pathogenesis of cardiovascular disease. Chronic heart failure is associated with oxidative stress in the myocardium and globally. Redox balance in the heart and brain is controlled, in part, by antioxidant proteins regulated by the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), which is reduced in the heart failure state. Nrf2 can, in turn, be regulated by a variety of mechanisms including circulating microRNAs (miRNAs) encapsulated in extracellular vesicles (EVs) derived from multiple cell types in the heart. Here, we review the role of the Nrf2 and antioxidant enzyme signaling pathway in mediating redox balance in the myocardium and the brain in the heart failure state. This review focuses on Nrf2 and antioxidant protein regulation in the heart and brain by miRNA-enriched EVs in the setting of heart failure. We discuss EV-mediated intra- and inter-organ communications especially, communication between the heart and brain via an EV pathway that mediates cardiac function and sympatho-excitation in heart failure. Importantly, we speculate how engineered EVs with specific miRNAs or antagomirs may be used in a therapeutic manner in heart failure.

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