Jun 12, 2019

Myocyte enhancer factor 2A delays vascular endothelial cell senescence by activating the PI3K/p-Akt/SIRT1 pathway

Aging
Benrong LiuShi-Ming Liu

Abstract

Myocyte enhancer factor 2A (MEF2A) dysfunction is closely related to the occurrence of senile diseases such as cardiocerebrovascular diseases, but the underlying molecular mechanism is unclear. Here, we studied the effects of MEF2A on the senescent phenotype of vascular endothelial cells (VEC) and downstream signaling pathway, and the association between plasma MEF2A levels and coronary artery disease (CAD). Results showed that MEF2A silencing promoted cell senescence and down-regulated PI3K/p-AKT/Sirtuin 1 (SIRT1) expression. MEF2A overexpression delayed cell senescence and up-regulated PI3K/p-AKT/SIRT1. Hydrogen peroxide (H2O2) treatment induced cellular senescence and down-regulated the expression of MEF2A and PI3K/p-AKT/SIRT1. MEF2A overexpression inhibited cellular senescence and the down-regulation of PI3K/p-AKT/SIRT1 induced by H2O2. Further study revealed that MEF2A directly up-regulated the expression of PIK3CA and PIK3CG through MEF2 binding sites in the promoter region. Pearson correlation and logistic regression analysis showed that the plasma level of MEF2A was negatively correlated with CAD, and with age in the controls. These results suggested that MEF2A can directly up-regulate PI3K gene expression, and one of t...Continue Reading

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Mentioned in this Paper

Biological Markers
Study
SIRT1 protein, human
Biochemical Pathway
SIRT1
Cell Aging
Hydrogen Peroxide
AKT1
Coronary Artery Disease
Vascular Endothelial Cells

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