Abnormal Endothelial Gene Expression Associated With Early Coronary Atherosclerosis

Area of Science:

• Cardiovascular Science
• Genetics
• Molecular Biology

Background:

• Early atherosclerosis risk is challenging to predict.
• Endothelial dysfunction is a key factor in atherosclerosis development.
• Heritable risk factors for atherosclerosis require further investigation.

Purpose of the Study:

• To assess the feasibility of using gene expression in endothelial cells to identify heritable risk for early atherosclerosis.
• To investigate the relationship between endothelial function and specific gene expression patterns.

Main Methods:

• Coronary reactivity testing was performed on subjects under 50 without obstructive coronary artery disease.
• Gene expression profiling of Blood Outgrowth Endothelial Cells (BOEC) was conducted using microarrays.
• Differential gene expression analysis focused on genes linked to endothelial function.

Main Results:

• A significant inverse correlation was found between high mobility group box 1 (HMGB1) and laminin gamma 1 (LAMC1) expression in subjects with abnormal endothelial function.
• Abnormal BOEC exhibited significantly higher HMGB1 release and lower LAMC1 deposition compared to normal BOEC.
• Clinical follow-up data were collected for subjects over several years.

Conclusions:

• The identified HMGB1/LAMC1 gene expression pattern may represent a heritable risk state for early coronary atherosclerosis.
• This pattern's predicted impact on the focal adhesion complex and endothelial shear responsiveness supports its pathogenic role.
• This gene expression analysis could enable early detection and intervention for atherosclerosis risk, even in childhood.