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

Abstract

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 (nϭ20), patients with hypertriglyceridemia and low HDL (nϭ39) had significantly increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) (316Ϯ28.8 versus 225Ϯ16.6 ng/mL), sVCAM-1 (743Ϯ52.2 versus 522Ϯ43.6 ng/mL), and soluble E-selectin (83Ϯ5.9 versus 49Ϯ3.6 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 Ն7 months, triglyceride level was reduced by 47Ϯ4.6%, sICAM-1 level was reduced by 9Ϯ3.4% (Pϭ.02), and soluble E-selectin level was reduced by 16Ϯ3.2% (PϽ.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-

Similarities and differences between the effects of EPA and DHA on markers of atherosclerosis in human subjects

“…02), and soluble E selectin (P = 0 . 0001), but did not change soluble VCAM-1 concentration (61) . In another study with type 2 diabetic patients, EPA (1 .…”

Coronary Vasomotor Function Is Abnormal in First-Degree Relatives of Patients With Type 2 Diabetes

“…Oxidative stress may also play a pathophysiological role in the endothelial dysfunction in first-degree relatives (18), although we did not measure parameters of it. On the other hand, it could be argued that the increase in sICAM-1, which is a marker of endothelial cell activation (7), could be secondary to subclinical CVD in first-degree relatives, a possibility consistent with evidence that concentrations of sICAM-1 are correlated with the degree of intima-media thickness (19), which is increased in first-degree relatives (20). Our study was not designed to compare the value of FMD and CFVR as early markers of cardiovascular risk in firstdegree relatives.…”

Induction of Atherosclerosis by Human Chylomicron Remnants: A Hypothesis

“…The expression of E-selectin, ICAM-1 and VCAM-1is relatively low in normal vascular cells and is upregulated in response to various stimuli, including cytokines and oxidants, thus enabling monocytes to adhere to the vessel wall. In vivo animal studies and immunohistochemical studies of human tissues have shown that these CAMs are expressed at increased levels in atherosclerotic plaques (47). The normal endothelium is characterized by the production of a number of molecules that affect the contractile state of adjacent myocytes and the behavior of formed elements within the blood stream, and by the absence of cell surface adhesion molecules.…”