Proliferation, migration and phenotypic transformation of VSMC induced via Hcy related to up-expression of WWP2 and p-STAT3

To provide a theoretical basis for the prevention and treatment of atherosclerosis (AS), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on regulating the proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMC) vi...

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Bibliographic Details
Published in:PloS one 2024-01, Vol.19 (1), p.e0296359-e0296359
Main Authors: Wang, Xiuyu, Gui, Na, Ma, Xing, Zeng, Yue, Mo, Tingrun, Zhang, Minghao
Format: Article
Language:English
Subjects:
Analysis
Animal models
Animals
Aorta - cytology
Apolipoprotein E
Apolipoproteins E - metabolism
Arteriosclerosis
Atherosclerosis
Atherosclerosis - metabolism
Atherosclerosis - pathology
Biology and Life Sciences
Biotechnology
Care and treatment
Cell Movement
Cell proliferation
Diagnosis
Extracellular matrix
Genetic transformation
Genotype & phenotype
Health aspects
Heart failure
Histone Demethylases - metabolism
Histones
Homocysteine
Homocystine - metabolism
Hypertension
Laboratory animals
Ligases
Male
Mice
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - pathology
Phenotype
Phenotypes
Phosphorylation
Physiology
Research and Analysis Methods
Signal Transduction
SIRT1 protein
Sirtuin 1 - metabolism
Smooth muscle
Stat3 protein
STAT3 Transcription Factor - metabolism
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - metabolism
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Summary:To provide a theoretical basis for the prevention and treatment of atherosclerosis (AS), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on regulating the proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMC) via sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) through Nedd4-like E3 ubiquitin-protein ligase WWP2 (WWP2). Here, Based on the establishment of ApoE-/- mouse models of high Hcy As and the model of Hcy stimulation of VSMC in vitro to observe the interaction between WWP2 and STAT3 and its effect on the proliferation, migration, and phenotypic transformation of Hcy-induced VSMC, which has not been previously reported. This study revealed that WWP2 could promote the proliferation, migration, and phenotype switch of Hcy-induced VSMC by up-regulating the phosphorylation of SIRT1/STAT3 signaling. Furthermore, Hcy might up-regulate WWP2 expression by inhibiting histone H3K27me3 expression through up-regulated UTX. These data suggest that WWP2 is a novel and important regulator of Hcy-induced VSMC proliferation, migration, and phenotypic transformation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0296359