VCAMs

VCAMs, or vascular cell adhesion molecules, are a family of immunoglobulin superfamily adhesion proteins primarily expressed on vascular endothelium. The best characterized member is VCAM-1 (CD106). VCAM-1 is a type I transmembrane glycoprotein with multiple immunoglobulin-like extracellular domains. Its expression is low in quiescent endothelium but is rapidly upregulated by cytokines such as TNF-α, IL-1, and endotoxins during inflammation, particularly in arteries and inflamed tissues. A soluble form, sVCAM-1, can be shed from the cell surface and serves as a circulating biomarker of endothelial activation.

Functionally, VCAM-1 mediates adhesion of leukocytes to vascular endothelium through binding of leukocyte integrins, notably VLA-4 (α4β1) and α4β7. This interaction supports firm adhesion and subsequent transmigration of immune cells into tissues, contributing to inflammatory responses and immune surveillance. VCAM-1 expression is implicated in the pathogenesis of several conditions, including atherosclerosis, transplant rejection, rheumatoid arthritis, and asthma. In cancer, VCAM-1–dependent adhesion can facilitate metastasis by promoting tumor cell arrest on endothelium.

Clinically, elevated sVCAM-1 levels are associated with cardiovascular risk and endothelial dysfunction. Therapies that interrupt VCAM-1–integrin interactions, such as anti-adhesion strategies, have been explored in inflammatory diseases; however, systemic blockade can produce adverse effects due to impaired immune cell trafficking. The VCAM family includes VCAM-1 and related endothelial adhesion molecules; the mouse ortholog is Vcam1.