Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells.
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).


RESULTS
VLDL CIII+ and LDL CIII+ (100 microg 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 microg/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 PKCalpha and RhoA in THP-1 cells, which resulted in beta1-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 PKCalpha and RhoA-mediated beta1-integrin activation. These results indicate that apoCIII not only modulates lipoprotein metabolism but also may directly contribute to the development of atherosclerosis.
Kawakami
Akio
A
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Aikawa
Masanori
M
Libby
Peter
P
Alcaide
Pilar
P
Luscinskas
Francis W
FW
Sacks
Frank M
FM
D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C / Q000502:physiology*; D050197:Atherosclerosis / Q000209:etiology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008074:Lipoproteins / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry; D009000:Monocytes / Q000166:cytology*; D051571:Protein Kinase C-alpha; D020742:rhoA GTP-Binding Protein
D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D019012:Integrin beta1; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C066737:RHOA protein, human; D051571:Protein Kinase C-alpha; D020742:rhoA GTP-Binding Protein