Adhesion Molecules: Master Controllers of the Circulatory System

Abstract

This manuscript will review our current understanding of cellular adhesion molecules (CAMs) relevant to the circulatory system, their physiological role in control of vascular homeostasis, innate and adaptive immune responses, and their importance in pathophysiological (disease) processes such as acute lung injury, atherosclerosis, and pulmonary hypertension. This is a complex and rapidly changing area of research that is incompletely understood. By design, we will begin with a brief overview of the structure and classification of the major groups of adhesion molecules and their physiological functions including cellular adhesion and signaling. The role of specific CAMs in the process of platelet aggregation and hemostasis and leukocyte adhesion and transendothelial migration will be reviewed as examples of the complex and cooperative interplay between CAMs during physiological and pathophysiological processes. The role of the endothelial glycocalyx and the glycobiology of this complex system related to inflammatory states such as sepsis will be reviewed. We will then focus on the role of adhesion molecules in the pathogenesis of specific disease processes involving the lungs and cardiovascular system. The potential of targeting adhesion molecules in the treatment of immune and inflammatory diseases will be highlighted in the relevant sections throughout the manuscript.

TRPV4—A Missing Link Between Mechanosensation and Immunity

“…An important additional role of TRPV4 in innate immunity relates to expression and function in the vascular endothelium, which by way of lining the inner surface of blood vessels and regulating cell adhesion and migration via expression of adhesion molecules acts as a gate keeper and controls the access for cells of the innate (and adaptive) immune system to sites of inflammation (61). TRPV4 activation in lung endothelial cells has been shown to increase vascular permeability (16,27,29), in part via disintegration of cell junctions (62) and degradation of ECM components and non-matrix components like integrins and VEcadherins by matrix metalloproteinases (MMPs) MMP2 and MMP9 (63), and in part by calmodulin-dependent activation of the endothelial contractile machinery (64).…”

Endothelial NOD1 directs myeloid cell recruitment in atherosclerosis through VCAM‐1

“…The most relevant ECAMs in leukocyte arrest belong to the Ig superfamily of adhesion molecules (Ig-CAMs). In this regard, endothelial VCAM 1 binds to the integrin cellsurface ligand very late antigen 4 (VLA-4) in monocytes and T cells preferably; meanwhile neutrophils use the endothelial intracellular adhesion molecule 1 (ICAM-1) to transiently bind to its ligand lymphocyte function-associated antigen 1 (2).…”

Fibroblast Growth Factor Signaling Mediates Pulmonary Endothelial Glycocalyx Reconstitution

“…The endothelial glycocalyx is a heparan sulfate (HS)-rich layer of glycosaminoglycans and associated proteoglycans that lines the microand macrovascular intima. In vivo, glycocalyx glycosaminoglycans become highly hydrated, forming a substantial gel-like endothelial surface layer (ESL) that projects 0.5 mm to over 10 mm into the vascular lumen (1). An intact ESL contributes to the endothelial barrier to fluid and protein, regulates leukocyte-endothelial adhesion, and transduces fluid shear stress into endothelial nitric oxide synthesis (2).…”