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(Circulation. 2006;113:691-700.)
© 2006 American Heart Association, Inc.

Molecular Cardiology

Apolipoprotein CIII in Apolipoprotein B Lipoproteins Enhances the Adhesion of Human Monocytic Cells to Endothelial Cells

Akio Kawakami, MD; Masanori Aikawa, MD, PhD; Peter Libby, MD; Pilar Alcaide, PhD; Francis W. Luscinskas, PhD; Frank M. Sacks, MD

From the Department of Nutrition, Harvard School of Public Health (A.K., F.M.S.), and Cardiovascular Medicine (M.A., P.L., F.M.S.) and Center for Excellence in Vascular Biology, Department of Pathology (P.A., F.W.L.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Frank M. Sacks, MD, Nutrition of Department, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail fsacks{at}hsph.harvard.edu

Received May 11, 2005; de novo received November 9, 2005; accepted November 29, 2005.

Background— Lipoproteins containing apolipoprotein (apo) CIII predict coronary heart disease and associate with components of the metabolic syndrome. ApoCIII inhibits lipoprotein catabolism in plasma. However, it is unknown whether apoCIII itself, or in association with VLDL, LDL, or HDL, directly affects atherogenic mechanisms in vascular cells. Thus, we investigated the direct effect of lipoproteins that do or do not have apoCIII, and apoCIII itself, on adhesion of THP-1 cells, a human monocytic cell line, to vascular endothelial cells (ECs).

Methods and Results— VLDL CIII⁺ and LDL CIII⁺ (100 µg apoB/mL) from fasting plasma of 18 normolipidemic volunteers increased THP-1 cell adhesion to ECs under static conditions by 2.4±0.3-fold and 1.8±0.7-fold, respectively (P<0.01), whereas VLDL or LDL without apoCIII did not affect THP-1 cell adhesion. ApoCIII (100 µg/mL), but not apoCI, apoCII or apoE, also increased THP-1 cell adhesion by 2.1±0.6-fold. Studies with human peripheral blood monocytes yielded similar results. ApoCIII also had strong proadhesive effects under shear flow conditions. VLDL CIII⁺, LDL CIII⁺, or apoCIII itself activated PKC and RhoA in THP-1 cells, which resulted in ß1-integrin activation and enhancement of THP-1 cell adhesion. Interestingly, HDL CIII⁺ did not affect THP-1 cell adhesion, whereas HDL without apoCIII decreased their adhesion.

Conclusions— ApoB lipoproteins that contain apoCIII increase THP-1 cell adhesion to ECs via PKC and RhoA-mediated ß1-integrin activation. These results indicate that apoCIII not only modulates lipoprotein metabolism but also may directly contribute to the development of atherosclerosis.

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