HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Biology
• Atherosclerosis Research

Background:

• Atherosclerosis predominantly affects arterial regions with disturbed blood flow.
• Stable blood flow (s-flow) offers protection against atherosclerosis through incompletely understood mechanisms.

Purpose of the Study:

• To identify genes involved in the atheroprotective effects of s-flow.
• To investigate the role of Heart-of-glass 1 (HEG1) in endothelial response to flow and atherosclerosis development.

Main Methods:

• Reanalyzed single-cell RNA-sequencing data to identify s-flow-induced genes.
• Studied HEG1 expression in mouse arteries and human endothelial/coronary artery cells.
• Utilized HEG1 knockdown and endothelial-specific knockout mice (HEG1^iECKO) in atherosclerosis models.

Main Results:

• S-flow upregulated HEG1 expression and promoted its translocation and release in endothelial cells.
• HEG1 knockdown impaired endothelial barrier function and increased monocyte adhesion, permeability, and migration.
• HEG1 deficiency exacerbated atherosclerosis in mice, increasing plaque complexity and inflammation.
• Endothelial HEG1 expression was reduced in human coronary arteries with advanced plaques.

Conclusions:

• HEG1 is a novel mediator of atheroprotective endothelial responses to blood flow.
• HEG1 plays a critical role in preventing atherosclerosis progression.
• HEG1 represents a potential therapeutic target for atherosclerosis.