Fluid shear stress modulates endothelial inflammation by targeting LIMS2

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Atherosclerosis Research

Background:

• Mechanosensitive genes are crucial in cardiovascular diseases.
• The specific role of flow-sensitive genes in atherosclerosis remains largely unexplored.
• Endothelial dysfunction is a key initiator of atherosclerosis.

Purpose of the Study:

• To identify novel mechanosensitive genes involved in cardiovascular pathophysiology.
• To investigate the role of flow-sensitive genes in the context of disturbed blood flow and atherosclerosis.
• To elucidate the molecular mechanisms by which disturbed flow impacts endothelial cells.

Main Methods:

• Utilized *in vitro* studies with human endothelial cells (ECs) exposed to disturbed flow (d-flow).
• Employed *in vivo* mouse models to assess gene expression changes under d-flow conditions.
• Analyzed the expression of LIM Zinc Finger Domain Containing 2 (LIMS2) and inflammatory markers (VCAM-1, ICAM-1).

Main Results:

• Identified LIM Zinc Finger Domain Containing 2 (LIMS2) as a novel mechanosensitive gene.
• Demonstrated that LIMS2 expression is downregulated by disturbed flow in both human ECs and mouse models.
• Showed that suppressed LIMS2 expression promotes endothelial inflammation by upregulating VCAM-1 and ICAM-1.

Conclusions:

• LIMS2 is a newly identified flow-sensitive gene implicated in endothelial inflammation.
• Disturbed flow-induced downregulation of LIMS2 contributes to the inflammatory processes underlying atherosclerosis.
• LIMS2 represents a potential therapeutic target for mitigating endothelial inflammation and treating atherosclerosis.