Soluble Cell Adhesion Molecules in Hypertriglyceridemia and Potential Significance on Monocyte Adhesion

From the Speros P. Martel Section of Leukocyte Biology, Department of Pediatrics (Y.A., C.W.S., C.M.B.) and Section of Atherosclerosis, Department of Medicine (B.E.-M., K.T.K., H.P., C.M.B.), Baylor College of Medicine, Houston, Tex; the Cardiovascular and Musculoskeletal Research Department, Zeneca Pharmaceuticals, Macclesfield, Alderley Park, UK (C.F.R.); and Pronova Biocare, Lysaker, Norway (K.O.).

Correspondence to Christie M. Ballantyne, MD, Baylor College of Medicine, 6565 Fannin, MS A-601, Houston, TX 77030. E-mail cmb{at}bcm.tmc.edu

Abstract—Hypertriglyceridemia may contribute to the development of atherosclerosis by increasing expression of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as markers for CAMs. In this study, we examined the association between sCAMs and other risk factors occurring with hypertriglyceridemia, the effect of triglyceride reduction on sCAM levels, and the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte adhesion in vitro. Compared with normal control subjects (n=20), patients with hypertriglyceridemia and low HDL (n=39) had significantly increased 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). ANCOVA showed that the higher sCAM levels in patients occurred independently of diabetes mellitus and other risk factors. In 27 patients who received purified n-3 fatty acid (Omacor) 4 g/d for 7 months, triglyceride level was reduced by 47±4.6%, sICAM-1 level was reduced by 9±3.4% (P=.02), and soluble E-selectin level was reduced by 16±3.2% (P<.0001), with the greatest reduction in diabetic patients. These results support previous in vitro data showing that disorders in triglyceride and HDL metabolism influence CAM expression and treatment with fish oils may alter vascular cell activation. In a parallel-plate flow chamber, recombinant sVCAM-1 at the concentration seen in patients significantly inhibited adhesion of monocytes to interleukin-1–stimulated cultured endothelial cells under conditions of flow by 27.5±7.2%. Thus, elevated sCAMs may negatively regulate monocyte adhesion.

Key Words: triglycerides • cell adhesion molecules • monocytes • endothelial cells

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