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

Area of Science:

• Molecular biology
• Cellular senescence
• Cardiovascular research

Background:

• Myocyte enhancer factor 2A (MEF2A) dysfunction is implicated in senile diseases like cardiocerebrovascular diseases.
• The precise molecular mechanisms linking MEF2A to cellular senescence and cardiovascular disease remain unclear.

Purpose of the Study:

• To investigate the role of MEF2A in vascular endothelial cell (VEC) senescence.
• To elucidate the downstream signaling pathways affected by MEF2A.
• To assess the association between plasma MEF2A levels and coronary artery disease (CAD).

Main Methods:

• MEF2A gene silencing and overexpression in VECs.
• Hydrogen peroxide (H2O2) induction of cellular senescence.
• Analysis of PI3K/p-AKT/Sirtuin 1 (SIRT1) pathway expression.
• Investigation of MEF2A binding to PIK3CA and PIK3CG promoters.
• Correlation and logistic regression analyses of plasma MEF2A levels with CAD and age.

Main Results:

• MEF2A silencing promoted VEC senescence and decreased PI3K/p-AKT/SIRT1 expression.
• MEF2A overexpression delayed senescence and increased PI3K/p-AKT/SIRT1 expression.
• H2O2-induced senescence was inhibited by MEF2A overexpression, which also restored PI3K/p-AKT/SIRT1 levels.
• MEF2A directly upregulated PIK3CA and PIK3CG gene expression.
• Plasma MEF2A levels showed a negative correlation with CAD and age in controls.

Conclusions:

• MEF2A directly enhances PI3K gene expression.
• MEF2A delays VEC senescence by activating SIRT1 expression via the PI3K/p-Akt pathway.
• Plasma MEF2A levels may serve as a potential biomarker for predicting CAD risk.