SOLUBLE CELL-ADHESION MOLECULES IN HYPERTRIGLYCERIDEMIA AND POTENTIALSIGNIFICANCE ON MONOCYTE ADHESION

Hypertriglyceridemia may contribute to the development of atherosclero sis by increasing expression of cell adhesion molecules (CAMs), Althou gh the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may s erve as markers for CAMs. In this study, we examined the association b etween sCAMs and other risk factors occurring with hypertriglyceridemi a, the effect of triglyceride reduction on sCAM levels, and the role o f soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte adhe sion in vitro. Compared with normal control subjects (n=20), patients with hypertriglyceridemia and low HDL (n=39) had significantly increas ed levels of soluble intercellular adhesion molecule-1 (sICAM-1) (316/-28.8 versus 225+/-16.6 ng/mL), sVCAM-1 (743+/-52.2 versus 522+/-43.6 ng/mL), and soluble E-selectin (83+/-5.9 versus 49+/-3.6 ng/mL). ANCO VA showed that the higher sCAM levels in patients occurred independent ly of diabetes mellitus and other risk factors, In 27 patients who rec eived purified n-3 fatty acid (Omacor) 4 g/d for greater than or equal to 7 months, triglyceride level was reduced by 47+/-4.6%, sICAM-1 lev el was reduced by 9+/-3.4% (P=.02), and soluble E-selectin level was r educed by 16+/-3.2% (P<.0001), with the greatest reduction in diabetic patients. These results support previous in vitro data showing that d isorders in triglyceride and HDL metabolism influence CAM expression a nd treatment with fish oils may alter vascular cell activation. In a p arallel-plate flow chamber, recombinant sVCAM-1 at the concentration s een in patients significantly inhibited adhesion of monocytes to inter leukin-1-stimulated cultured endothelial cells under conditions of flo w by 27.5 +/- 7.2%. Thus, elevated sCAMs may negatively regulate monoc yte adhesion.