Atherosclerosis is a progressive, chronic inflammatory disease of large arteries in which lesions preferentially occur at vessel sites exposed to rapid changes in blood flow. Low density lipoprotein (LDL) deposition and leukocyte infiltration leads to plaque formation and narrowing of the artery (stenosis), which restricts blood flow and causes angina. Atherosclerosis can also induce thrombus formation if lipids from plaques come into contact with blood, and plaque associated weakening of artery walls can lead to eventual rupture (aneurysm).

PECAM-1 is a membrane protein expressed on the surface of many cells in the blood, as well as the endothelial cells lining blood vessels. PECAM-1 participates in the adhesion cascade necessary for leukocyte extravasation and serves as a sensor responding to changes in mechanical shear force that result from changes in blood flow.

In this report, the authors determine that PECAM-1 induces susceptibility to atherosclerosis. Using mice deficient in the cell adhesion molecule PECAM-1 (PECAM-1−/−), researchers found a 50–60% reduction of atherosclerotic lesions in the aortae of mice with a genetic susceptibility to atherosclerosis (ApoE−/−). Since some athlerosclerotic lesions are found in PECAM-1−/− animals, it is likely that the absence of PECAM-1 is not completely preventative, but delays the onset of pathology.

PECAM-1 functions in processes of inflammation and in the sensing of shear stress related to blood flow. It is possible that one or both of these processes contribute to the development and progression of atherosclerosis, suggesting that PECAM-1 is a potential candidate for drug targeting to limit the disease process.

2008