Endothelial primary cilia inhibit atherosclerosis.

Area of Science:

• Cell Biology
• Cardiovascular Research
• Biomedical Science

Background:

• Primary cilia are microtubule-based cellular projections crucial for intercellular signaling.
• Endothelial cells possess primary cilia that may function as mechanosensors of blood flow.
• The role of endothelial cilia in vascular physiology and disease remains largely unexplored.

Purpose of the Study:

• To investigate the in vivo function of primary cilia in endothelial cells.
• To determine the role of endothelial cilia in vascular development and atherosclerosis.
• To elucidate the molecular mechanisms by which endothelial cilia influence atherosclerotic plaque formation.

Main Methods:

• Conditional deletion of Ift88, a ciliogenesis gene, in mouse endothelial cells.
• Analysis of vascular development in knockout mice.
• Induction of atherosclerosis using a high-fat, high-cholesterol diet in Apoe(-/-) mice.
• Assessment of atherosclerotic plaque burden, inflammatory gene expression, and eNOS activity.

Main Results:

• Endothelial primary cilia are dispensable for mammalian vascular development.
• Cilia are enriched at aortic branch points and high-curvature sites, which are prone to atherosclerosis.
• Deletion of endothelial cilia exacerbated atherosclerosis in Apoe(-/-) mice.
• Loss of endothelial cilia led to increased inflammatory gene expression and decreased eNOS activity.

Conclusions:

• Endothelial primary cilia are not essential for vascular development but play a protective role against atherosclerosis.
• Endothelial cilia inhibit pro-atherosclerotic signaling pathways, likely through modulation of inflammation and eNOS activity.
• Targeting endothelial cilia may offer a novel therapeutic strategy for preventing or treating atherosclerosis.