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 PKCα and RhoA in THP-1 cells, which resulted in β1-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 PKCα and RhoA-mediated β1-integrin activation. These results indicate that apoCIII not only modulates lipoprotein metabolism but also may directly contribute to the development of atherosclerosis.