Hcy regulates SIRT1-STAT3 phosphorylation by upregulating WWP2 expression and induce VSMCs proliferation, migration, and phenotypic switch

Autor: Xiuyu Wang, Xing Ma, Yue Zeng, Smritee Pokharel, minghao zhang
Rok vydání: 2023
Popis: The proliferation, migration, and cellular morphology of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis (AS). Homocysteine (Hcy) is a sulfur-containing amino acid, which is an intermediate product of methionine metabolism. Hcy can induce proliferation, migration, and phenotypic switch of VSMCs, but details of these mechanisms are still unclear. NAD-dependent deacetylase sirtuin-1 (SIRT1-STAT3) signaling pathway is involved in various cellular functions. Here, we sought to determine if this multifunctional pathway played a role in Hcy-induced proliferation, migration, and phenotypic transformation of VSMCs, which has not been previously reported. NEDD4-like E3 ubiquitin-protein ligase WWP2 (WWP2) is involved in VSMCs phenotypic modulation and can be a potential target in the treatment of various cardiovascular diseases. In our study, Serum Hcy of the ApoE-/-mice fed 2% high-methionine diet was significantly higher than that of the normal diet group (P -/-+HMD mouse showed changes in the expression level of aortic proteins, α-SMA and SM22α were decreased (P P P -/-+HMD. In vitro, WWP2 mRNA and protein expressions were higher in the Hcy group (P P P P P
Databáze: OpenAIRE