Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology

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• 作者：Dimitry A. Chistiakov^a ; Alexander N. Orekhov^b ; ^c ; ^d ; Yuri V. Bobryshev^b ; ^e ; ^f ; ^{y.bobryshev@unsw.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Endothelial cell adhesion molecules ; Platelet endothelial cell adhesion molecule-1 ; PECAM-1 ; Endothelial barrier function ; Vascular physiology Atherosclerosis ; Inflammation
• 刊名：Experimental and Molecular Pathology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：100
• 期：3
• 页码：409-415
• 全文大小：1333 K

文摘

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.