Alpha-lipoic Acid Protects Against Pressure Overload-induced Heart Failure Via ALDH2-dependent Nrf1-FUNDC1 Signaling

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Aug 1

PMID 32732978

Citations 32

Authors

Wenjia Li

Lei Yin

Xiaolei Sun

Jian Wu

Zhen Dong

Kai Hu

Aijun Sun

Junbo Ge

Affiliations

Soon will be listed here.

Abstract

Alpha-lipoic acid (α-LA), a well-known antioxidant, was proved to active ALDH2 in nitrate tolerance and diabetic animal model. However, the therapeutic advantage of α-LA for heart failure and related signaling pathway have not been explored. This study was designed to examine the role of α-LA-ALDH2 in heart failure injury and mitochondrial damage. ALDH2 knockout (ALDH2) mice and primary neonatal rat cardiomyocytes (NRCMs) were subjected to assessment of myocardial function and mitochondrial autophagy. Our data demonstrated α-LA significantly reduced the degree of TAC-induced LV hypertrophy and dysfunction in wild-type mice, not in ALDH2 mice. In molecular level, α-LA significantly restored ALDH2 activity and expression as well as increased the expression of a novel mitophagy receptor protein FUNDC1 in wild-type TAC mice. Besides, we confirmed that ALDH2 which was activated by α-LA governed the activation of Nrf1-FUNDC1 cascade. Our data suggest that α-LA played a positive role in protecting the heart against adverse effects of chronic pressure overload.

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