title: Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology.
abstract: Platelet endothelial cell adhesion molecule (PECAM-1) is highly expressed in vascular cells such as endothelial cells (ECs) and blood-borne cells like platelets and leukocytes. In ECs, this molecule controls junctional and adhesive properties. In physiological conditions, PECAM-1 supports the endothelial barrier function. In inflammation that is observed in vessels affected by atherosclerosis, the function of PECAM-1 is impaired, an event that leads to increased adhesion of neutrophils and other leukocytes to ECs, decreased vascular integrity, and higher leukocyte transmigration to the intima media. PECAM-1 has six extracellular immunoglobulin (Ig)-like domains that support attraction and adhesion of leukocytes to ECs. The cytoplasmic tail of PECAM-1 contains two tyrosine residues (Tyr-663 and Tyr-686) that could be phosphorylated by Src family protein kinases is involved in the intracellular signaling. Actually, those tyrosines are the part of the immunoreceptor tyrosine-based inhibition motifs (ITIMs) that inhibit inflammation. However, in atherosclerosis, the PECAM-1-dependent immune suppression is disturbed. This in turn facilitates recruitment of leukocytes and supports proatherogenic inflammation.
authors.affiliation: Department of Molecular Genetic Diagnostics and Cell Biology, Institute of Pediatrics, Research Center for Children's Health, 119991 Moscow, Russia.
authors.forename: Dimitry A
authors.initials: DA
authors.lastname: Chistiakov
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia; Institute for Atherosclerosis, Skolkovo Innovative Center, Moscow 143025, Russia; Department of Biophysics, Biological Faculty, Moscow State University, Moscow 119991, Russia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Orekhov
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia; Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, Sydney, NSW 2052, Australia; School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia. Electronic address: y.bobryshev@unsw.edu.au.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D001792:Blood Platelets / Q000378:metabolism; D002450:Cell Communication; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007962:Leukocytes / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: Endothelial barrier function; Endothelial cell adhesion molecules; Inflammation; PECAM-1; Platelet endothelial cell adhesion molecule-1; Vascular physiology Atherosclerosis