Correlation between insulin-induced estrogen receptor methylation and atherosclerosis

Area of Science:

• Cardiovascular Biology
• Endocrinology
• Molecular Medicine

Background:

• Hyperinsulinemia and insulin resistance are emerging causes of atherosclerosis.
• Estrogen receptor expression is linked to atherosclerosis incidence.
• Investigating the interplay between insulin and estrogen receptor alpha (ER-α) in atherosclerosis is crucial.

Purpose of the Study:

• To elucidate the effects of insulin and ER-α on atherosclerosis.
• To determine the molecular mechanisms by which insulin influences ER-α expression and vascular cell function.

Main Methods:

• Utilized ApoE/Lepr double knockout mice treated with insulin, followed by aortic analysis.
• Examined insulin's effects on vascular smooth muscle cells (VSMCs) in vitro, including gene expression and proliferation.
• Assessed ER-α gene methylation using bisulfite sequencing PCR.

Main Results:

• Insulin administration induced atherosclerosis formation in mice.
• Insulin increased DNA methyltransferase expression and decreased ER-α expression in VSMCs.
• Insulin treatment led to increased methylation of the ER-α gene in VSMCs, inhibiting proliferation.

Conclusions:

• Insulin promotes atherosclerosis by upregulating DNA methyltransferases, leading to ER-α gene methylation and reduced ER-α expression.
• This mechanism interferes with estrogen's regulation of VSMCs proliferation, contributing to atherosclerosis.
• Targeting insulin-induced methylation pathways may offer therapeutic strategies for atherosclerosis.