Endothelial Junctional Adhesion Molecule-a Guides Monocytes Into Flow-dependent Predilection Sites of Atherosclerosis

Background—Junctional adhesion molecule (JAM)-A expressed in endothelial, epithelial, and blood cells can regulate permeability and leukocyte extravasation. Atherosclerosis develops at sites of disturbed flow in large arteries, but the mechanisms guiding inflammatory cells into these predilection sites remain unknown. Methods and Results—To characterize cell-specific functions of JAM-A in atherosclerosis, we used apolipoprotein E–deficient mice with a somatic or endothelium-specific deficiency in JAM-A and bone marrow chimeras with JAM-A–deficient leukocytes. We show that impaired JAM-A expression in endothelial cells reduced mononuclear cell recruitment into the arterial wall and limited atherosclerotic lesion formation in hyperlipidemic mice. In contrast, JAM-A deficiency in bone marrow cells impeded monocyte de-adhesion, thereby increasing vascular permeability and lesion formation, whereas somatic JAM-A deletion revealed no significant effects. Regions with disturbed flow displayed a focal enrichment ...