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Differential associations between soluble cellular adhesion molecules and atherosclerosis in the Dallas Heart Study: a distinct role for soluble endothelial cell-selective adhesion molecule.

ABSTRACT: Endothelial cell-selective adhesion molecule (ESAM) is a junctional-type cellular adhesion molecule (CAM) that is uniquely expressed in vascular endothelium and activated platelets and mediates neutrophil and monocyte diapedesis across the endothelium. Given its role in endothelial pathobiology, we hypothesized that soluble ESAM (sESAM) would be independently associated with atherosclerosis and vascular stiffness.We measured sESAM, soluble intercellular adhesion molecule (sICAM)-1, and soluble vascular cell adhesion molecule (sVCAM)-1 in 3222 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcium (CAC) was measured by electron beam computed tomography, and abdominal aortic wall thickness (AWT), aortic plaque burden (APB), and aortic compliance (AC) by MRI. Increasing levels of sESAM were associated with all major cardiovascular risk factors as well as with inflammatory markers such as monocyte chemoattractant protein-1, but only weakly correlated with sICAM-1 and sVCAM-1. In multivariate analyses, sESAM was independently associated with prevalent CAC (OR 1.2 per SD increase, 95% CI 1.1 to 1.3; P=0.005), AWT (P=0.035), and AC (P=0.006), but not APB (P=0.15). In contrast, no independent associations were observed between sICAM-1 or sVCAM-1 and any of the atherosclerosis phenotypes.In this first reported clinical study of sESAM in humans, sESAM levels were independently associated with CAC, AWT, and AC, whereas sICAM-1 and sVCAM-1 were not. These findings support a unique role of this cellular adhesion molecule in atherosclerosis and suggest the need for further exploration of sESAM as a predictive biomarker and potential mediator of atherosclerosis.

SUBMITTER: Rohatgi A

PROVIDER: S-EPMC2771407 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Differential associations between soluble cellular adhesion molecules and atherosclerosis in the Dallas Heart Study: a distinct role for soluble endothelial cell-selective adhesion molecule.

Rohatgi Anand A Owens Andrew W AW Khera Amit A Ayers Colby R CR Banks Kamakki K Das Sandeep R SR Berry Jarett D JD McGuire Darren K DK de Lemos James A JA

Arteriosclerosis, thrombosis, and vascular biology 20091001 10

<h4>Objective</h4>Endothelial cell-selective adhesion molecule (ESAM) is a junctional-type cellular adhesion molecule (CAM) that is uniquely expressed in vascular endothelium and activated platelets and mediates neutrophil and monocyte diapedesis across the endothelium. Given its role in endothelial pathobiology, we hypothesized that soluble ESAM (sESAM) would be independently associated with atherosclerosis and vascular stiffness.<h4>Methods and results</h4>We measured sESAM, soluble intercellu ...[more]

PMID: 19759376

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Project description:OBJECTIVE:The objective of this study was to determine the profiles of maternal plasma soluble adhesion molecules in patients with preeclampsia, small-for-gestational-age (SGA) fetuses, acute pyelonephritis, preterm labor with intact membranes (PTL), preterm prelabor rupture of the membranes (preterm PROM), and fetal death. MATERIALS AND METHODS:A cross-sectional study was conducted to determine maternal plasma concentrations of sE-selectin, sL-selectin, and sP-selectin as well as sICAM-1, sVCAM-1, and sPECAM-1 in patients with (1) an uncomplicated pregnancy (control, n?=?100); (2) preeclampsia (n?=?94); (3) SGA fetuses (in women without preeclampsia/hypertension, n?=?45); (4) acute pyelonephritis (n?=?25); (5) PTL (n?=?53); (6) preterm PROM (n?=?24); and (7) fetal death (n?=?34). Concentrations of soluble adhesion molecules and inflammatory cytokines (tumor necrosis factor (TNF)-? and interleukin (IL)-8) were determined with sensitive and specific enzyme-linked immunoassays. RESULTS:In comparison to women with a normal pregnancy, (1) women with preeclampsia had higher median concentrations of sE-selectin, sP-selectin, and sVCAM-1, and a lower concentration of sL-selectin (all p values?<?.001); (2) patients with SGA fetuses had higher median concentrations of sE-selectin, sP-selectin, and sVCAM-1 (all p values?<?.05); (3) patients with a fetal death had higher median concentrations of sE-selectin and sP-selectin (all p values?<?.05); (4) patients with acute pyelonephritis had higher median plasma concentrations of sE-selectin, sICAM-1, and sVCAM-1 (all p values?<?.001); (5) patients with preeclampsia and acute pyelonephritis, plasma concentrations of sVCAM-1, sE-selectin, and sP-selectin correlated with those of the proinflammatory cytokines TNF-? and interleukin (IL)-8 (all p values?<?.05); (6) patients with PTL had a higher median concentration of sP-selectin and a lower median concentration of VCAM-1 (all p values <?.05); and (7) women with preterm PROM had lower median concentrations of sL-selectin and sVCAM-1 (all p values?<?.05). CONCLUSIONS:The results of this study show that endothelial cell activation/dysfunction reflected by the plasma concentration of sE-selectin is not specific to preeclampsia but is present in pregnancies complicated by SGA fetuses, acute pyelonephritis, and fetal death. Collectively, we report that each obstetrical syndrome appears to have a stereotypical profile of soluble adhesion molecules in the peripheral circulation.

Dataset Information

Differential associations between soluble cellular adhesion molecules and atherosclerosis in the Dallas Heart Study: a distinct role for soluble endothelial cell-selective adhesion molecule.

Publications

Differential associations between soluble cellular adhesion molecules and atherosclerosis in the Dallas Heart Study: a distinct role for soluble endothelial cell-selective adhesion molecule.

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