Soluble ICAM‐1 and VCAM‐1 as Markers of Endothelial Activation

Abstract

Activated endothelium releases the soluble adhesion molecules vascular cell adhesion molecule‐1 (sVCAM‐1) and intercellular adhesion molecule‐1 (sICAM‐1). Measurement of fluid‐phase adhesion molecules is therefore used to quantify endothelial activation, but it is unclear which is the better marker. The aims of the study were to compare the relationships between mRNA, surface and total expression and released VCAM‐1 and ICAM‐1 in endothelial cell cultures during activation, and to compare human umbilical vein endothelial cells (HUVEC) with the microvascular cell line HMEC‐1. sVCAM‐1 better represented mRNA and surface expression changes in HUVEC undergoing endotoxin stimulation than did sICAM‐1. Very little VCAM‐1 was released from endotoxin‐stimulated HMEC‐1, and sICAM‐1 seemed a better activation marker for these cells. During incubation of HUVEC in media with glucose concentrations of 5.6, 10.6 or 20.6 mm, VCAM‐1 was released to the media in a dose‐dependent way without changes in surface expression. ICAM‐1 was not influenced by the glucose concentration. There are situations when VCAM‐1 concentrations in the media do not mirror the surface expression on HUVEC in culture, indicating that measurements of soluble adhesion molecules may not necessarily be representative of the conditions on the cell surface. Endothelium from different locations showed varying responses with respect to VCAM‐1 and ICAM‐1 liberation upon endotoxin stimulation. Thus, both sVCAM‐1 and sICAM‐1 should be quantified in clinical studies of endothelial activation until their characteristics are better clarified.

A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase

“…To address this point, we determined the effect of 12-HETE injection on retinal levels of ICAM-1 and VCAM-1, well-established markers of endothelial dysfunction in infl ammatory conditions ( 35 ). Western blot analysis of ICAM-1 showed a 2.9-fold increase in 12-HETE-injected eyes compared with vehicle-injected contralateral eyes.…”

Tissue-Specific Microvascular Endothelial Cells Show Distinct Capacity To Activate NK Cells: Implications for the Pathophysiology of Granulomatosis with Polyangiitis

“…Soluble forms of adhesion molecules (sICAM-1, sVCAM-1) have been found in the culture supernatant of cytokine-treated ECs (17,19,28). These soluble molecules may act as competitive inhibitors blocking adhesion to inflamed vascular endothelium, or they may modify leukocyte activation (29)(30)(31)(32)(33).…”

Alpha-Tocopherol and BAY 11-7082 Reduce Vascular Cell Adhesion Molecule in Human Aortic Endothelial Cells

“…The microvascular cell line HMEC-1 is reportedly one of the endothelial cell lines most similar to primary endothelium [21]. Results of sVCAM-1 in HMEC-1 cultures have shown wider variation than those from HUVEC experiments, and it is mainly for this reason that HUVECs have been used extensively in in vitro endothelium studies [45]. It is not clear, however, whether these differences render HMEC-1 a better or a poorer model of local inflammation than HUVECs.…”

“…It is not clear, however, whether these differences render HMEC-1 a better or a poorer model of local inflammation than HUVECs. However, HUVECs provide more consistent results even if genetic differences between donors may result in wider variation in the expression of inflammation markers [45]. Further cell culture studies are required using HMEC-1 or human coronary artery endothelial cells to confirm the sVCAM-1 results that had been observed in HAECs [38].…”