Potential risk of hyperuricemia: leading cardiomyocyte hypertrophy by inducing autophagy.
Year: 2020
Type: article
Abstract: BACKGROUND: Clinical studies have shown that hyperuricemia is associated with many cardiovascular diseases; however, the mechanisms involved remain unclear. In this study, we investigated the effect of uric acid on cardiomyocytes and the underlying mechanism. METHODS AND RESULTS: , which are involved in myocardial hypertrophy, and the relative cell surface area of cardiomyocytes in a dose-dependent manner. Consistently, the ratio of LC3II/I, which is a biomarker of autophagy, increased dose-dependently, whereas the protein level of p62, a protein that is degraded by autophagy, decreased. 3-MA, an autophagy inhibitor, rescued uric acid-induced myocardial hypertrophy. Treatment with uric acid increased the level of phosphorylated adenosine monophosphate kinase (AMPK), as well as its downstream effector unc-51-like kinase (ULK1). Pharmacological inhibition of AMPK by Compound C attenuated the uric acid-induced activation of autophagy and myocardial hypertrophy. CONCLUSIONS: Uric acid induces myocardial hypertrophy by activating autophagy via the AMPK-ULK1 signaling pathway. Decreasing the serum uric acid level may therefore be clinically beneficial in alleviating cardiac hypertrophy.
Source: PubMed
Authors: Xiao-Jie Zhang, Dong-Mei Liu, Ying Sun, Yan-Shan Li, Li-Li Ma, Xiu-Fang Kong, Xiao-Meng Cui, Rong-Yi Chen, Zhuo-Jun Zhang, Lin-Di Jiang
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3033338094