Associates' Presentations
| Intro | Prev | Next | Last |
Homocysteine increases monocyte adhesion to human endothelial cells via a cyclooxygenase-dependent mechanism.
R.J. Tumuluri, M.D. (Associate), M.D. Silverman, M.Sci, and P.I. Lelkes, Ph.D. Sinai Samaritan Medical Center, Departments of Medicine and Cell Biology, Milwaukee WI 53201
Elevated plasma homocysteine (HC) has been recently recognized as an independent risk factor for the development of atherosclerosis. Monocyte adhesion to, and subsequent migration through, the endothelial cell lining of the vascular lumen is a pivotal early event in the generation of atherosclerotic plaques. We hypothesized that HC can modulate monocyte/endothelial cell interactions by altering endothelial cell surface expression of cell adhesion molecules. We incubated confluent monolayers of human aortic endothelial cells (AEC) with various concentrations of HC (0-1000 M) for up to 24 hrs, and measured adhesion of subsequently seeded human monocytic U-937 cells. After culturing AEC in the presence of physiological levels of HC (i.e. 10 M), monocyte adhesion was not significantly different from that in untreated controls (p>0.114, n=5). At higher HC concentrations that are representative of in vivo pathological plasma levels, however, we observed a marked increase in monocyte adhesion to AEC. With 30 M HC, monocyte adhesion to AEC was elevated to levels 248 ? 35% of that seen with untreated controls (p=0.014, n=3). This effect was maximal at 100 M HC (302? 43% of control values, p=0.002, n=5), maintained through 300 M HC, and began to decrease at 1 mM HC, a concentration at which AEC cytotoxicity became evident. Concomitant incubation of AEC with 100 M HC and either 10 M indomethacin or 10 M aspirin decreased monocyte adhesion to a level not significantly different from that in untreated controls (p>0.8, n=3). In conclusion, HC increases monocyte adhesion to cultured AEC in a dose-dependent fashion, which is ameliorated by clinically relevant concentrations of cyclooxygenase pathway inhibitors. These data suggest a casual link between elevated plasma HC levels and the subendothelial accumulation of monocytes which is a hallmark of atherogenesis. We are currently investigating potential involvement of endothelial ICAM-1 and VCAM-1 expression in mediating these effects. Further work is warranted to determine whether these mechanisms operate in the in vivo scenario.
| Intro | Prev | Next | Last |
What's New
Contact Information
Sharon Haase, MD, FACP
Chapter Governor
Kelly Lang
Chapter Support Staff
Ph: 414-755-6280
E-mail: lang@svinicki.com