The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development

Area of Science:

• Cardiovascular science
• Epigenetics
• Molecular biology

Background:

• Cardiovascular disease (CVD), including atherosclerosis, is a leading cause of death.
• Atherosclerosis involves arterial thickening and is linked to DNA methylation changes in vascular cells.
• Endothelial dysfunction (ED) is an early atherosclerosis marker, potentially driven by endothelial DNA methylation alterations.

Purpose of the Study:

• To review evidence linking environmental risk factors to endothelial DNA methylation changes.
• To explore how these epigenetic alterations contribute to endothelial dysfunction and CVD.
• To consider the mechanisms by which risk factors affect DNA methylation regulators (DNMTs and TETs).

Main Methods:

• Literature review of studies on environmental risk factors and endothelial epigenetics.
• Analysis of molecular mechanisms affecting DNA methyltransferases (DNMTs) and Ten Eleven Translocases (TETs).
• Discussion of the role of oxygen, alpha-ketoglutarate, and iron in TET protein activity.

Main Results:

• Environmental factors (diabetes, smoking, hypertension, etc.) modify the endothelial methylome.
• These modifications alter gene transcription and endothelial cell function.
• TET protein activity is sensitive to hypoxia, metabolic state, and redox, influencing the methylome.

Conclusions:

• Modifiable risk factors significantly impact endothelial DNA methylation patterns.
• Changes in the endothelial methylome, influenced by risk factors, are implicated in ED and CVD.
• Understanding these epigenetic mechanisms offers potential therapeutic targets for CVD prevention.