SASH1, a new potential link between smoking and atherosclerosis

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Vascular Cell Biology

Background:

• Smoking is a major risk factor for atherosclerosis.
• SASH1 expression is elevated in monocytes of smokers and correlates with carotid plaque burden.
• The role of SASH1 in the vascular wall and its direct link to smoking-induced atherosclerosis requires further investigation.

Purpose of the Study:

• To validate the association between smoking, SASH1 expression, and atherosclerosis within the vascular wall.
• To determine the impact of SASH1 on endothelial cell functions, including migration, proliferation, and angiogenesis.

Main Methods:

• Analysis of SASH1 expression in human carotid arteries from smokers and non-smokers using gene expression and immunostaining.
• SASH1 knockdown in human aortic endothelial cells (HAECs) via siRNA.
• Assessment of HAEC functions (migration, proliferation, angiogenesis) and transcriptomic profiling after SASH1 silencing.

Main Results:

• SASH1 is expressed in vascular cells and macrophages; its expression is significantly higher in atherosclerotic carotids of smokers.
• SASH1 knockdown in HAECs led to increased cell migration, proliferation, and angiogenesis.
• SASH1 silencing decreased CYP1A1 expression, potentially via TP53 inhibition.

Conclusions:

• SASH1 expression is elevated in the atherosclerotic carotids of smokers.
• SASH1 silencing impacts endothelial angiogenic functions, suggesting a role in smoking-related atherosclerosis.
• This study provides a potential molecular link between smoking and atherosclerosis mediated by SASH1.