Priming effect of homocysteine on inducible vascular cell adhesion molecule-1 expression in endothelial cells.

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Chantal SéguinWilliam C Aird

Abstract

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis, as well as for arterial and venous thrombosis. However, the mechanisms through which elevated circulating levels of homocysteine cause vascular injury and promote thrombosis remain unclear. Here, we tested the hypothesis that homocysteine (Hcy) sensitizes endothelial cells to the effect of inflammatory mediators. Human umbilical vein endothelial cells (HUVEC) were incubated with Hcy 1.0 mM for varying time points, and then treated in the absence or presence of 1.5 U/ml thrombin or 10 mg/ml lipopolysaccharide (LPS). Hcy alone had no effect on the expression of vascular cell adhesion molecule (VCAM)-1. However, Hcy enhanced thrombin- and LPS-mediated induction of VCAM-1 mRNA and protein levels. Consistent with these results, pretreatment of HUVEC with Hcy resulted in a two-fold increase in LSP-mediated induction of leukocyte adhesion. The latter effect was significantly inhibited by anti-VCAM-1 antibodies. Together, these findings suggest that Hcy sensitizes HUVEC to the effect of inflammatory mediators thrombin and LPS, at least in part through VCAM-1 expression and function.

References

Jun 1, 1986·The Journal of Clinical Investigation·G M Rodgers, W H Kane
Oct 4, 1995·JAMA : the Journal of the American Medical Association·C J BousheyA G Motulsky
Aug 23, 2000·The Journal of Clinical Investigation·R T EberhardtJ Loscalzo
May 26, 2001·The Journal of Clinical Investigation·M I CybulskyD S Milstone
Oct 20, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M R AbidW C Aird
May 8, 2004·Stroke; a Journal of Cerebral Circulation·Anetta UndasHieronim Jakubowski
Aug 3, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Elizabeth O HarringtonSharon Rounds
Dec 14, 2004·European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes·D NolteK Messmer
Jan 27, 2005·Journal of Thrombosis and Haemostasis : JTH·M Den HeijerR Clarke
Sep 21, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Youichiro WadaWilliam C Aird
May 17, 2006·The Journal of Experimental Medicine·Kiichiro YanoWilliam C Aird
Oct 17, 2007·Clinical Chemistry and Laboratory Medicine : CCLM·Hieronim Jakubowski

❮ Previous
Next ❯

Related Concepts

Related Feeds

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cell Adhesion Molecules in AS

Cell adhesion molecules expressed on the vascular endothelium and circulating leukocytes in response to inflammatory stimuli are implicated in atherosclerosis. Here is the latest research.