Homocysteine induces vascular inflammatory response via SMAD7 hypermethylation in human umbilical vein smooth muscle cells

Microvascular Research
Lihua WeiYuan-Yuan Li

Abstract

Homocysteine (Hcy) can induce atherosclerosis through the inflammatory response and DNA methylation disorder. Our recent study has reported a novel epigenetic modified gene related to atherosclerosis -SMAD7. To further understand the pathogenesis of atherosclerosis, the current study was designed to investigate an inflammatory role of Hcy in human umbilical vein smooth muscle cells (HUVSMCs) through interfering with SMAD7 methylation. Using MALDI-TOF MS, we found that Hcy increased DNA methylation levels of SMAD7 promoter in a dose and time-dependent manner in HUVSMCs. Meanwhile, both SMAD7 mRNA and protein levels were decreased along with the increase of Hcy concentrations and treating time. Decreased SMAD7 levels led to up regulation of pro-inflammatory cytokines (TNF-α and IL-1β) expression in HUVSMCs. Furthermore, we found that activation of NF-κB pathway was the mechanism by which reduced Smad7 levels enhanced vascular inflammation. Thus, Hcy is able to activate NF-κB-mediated vascular inflammatory response via inducing hypermethylation of SMAD7 promoter in HUVSMCs. The in vitro findings supplement our recent clinical study that SMAD7 methylation as a novel marker in atherosclerosis and further elucidate the role of Hcy in...Continue Reading

Citations

Aug 9, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Jia ShiFan He
Sep 3, 2020·Heart, Lung & Circulation·Mingchang PangLihua Li
Feb 2, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Magy SallamAn Aerts

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