Native and gamma radiolysis-oxidized lipoprotein(a) increase the adhesiveness of rabbit aortic endothelium.
Accumulation of monocyte-derived foam cells in the arterial intima is a major event in the development of atherogenesis. We have examined whether native and oxidized lipoprotein(a) (Lp(a)) can induce adhesion of monocytic cells to aortic endothelium. The extensive oxidation of paired samples of Lp(a) and low-density lipoprotein (LDL) was achieved by O2.-/OH. free radicals produced by gamma radiolysis of water, leading to similar values for the formation of peroxidation markers (conjugated dienes, TBARS, 8-epi-PGF2alpha) for both Lp(a) and LDL. Rabbit aortic segments were incubated for 5 h in the presence of equimolar concentrations of native and oxidized preparations of Lp(a) and LDL (125 micromol cholesterol/l, corresponding to 40 and 30 mg protein/l for Lp(a) and LDL, respectively). The aortic segments were incubated with rhodamin-isothiocyanate labeled U937 monocytic cells for 30 min and cell adhesion was quantified by fluorescent microscopy. Native Lp(a), and to a larger extent oxidized Lp(a), significantly increased U937 cell adhesion by 2.3 and 2.7 fold compared to controls (P < 0.005 and P < 0.001, respectively). Monocytic cell adhesion was also increased by native LDL (1.6 fold, P < 0.005), and to a greater extent by oxidized LDL (2.3 fold, P < 0.001). Thus native Lp(a) enhances the adhesive properties of the arterial endothelium which may account for its proatherogenic action. Furthermore, our results show that oxidized Lp(a), as well as oxidized LDL, are potent stimuli of monocyte adhesion to endothelial cells.
Beaudeux
J L
JL
Laboratoire de Biochimie, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France. jean-louis.beaudeux@psl.ap-hop-paris.fr
Césarini
M L
ML
Gardès-Albert
M
M
Maclouf
J
J
Merval
R
R
Esposito
B
B
Peynet
J
J
Tedgui
A
A
D000818:Animals; D001013:Aorta, Thoracic; D001161:Arteriosclerosis / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005609:Free Radicals; D005720:Gamma Rays; D015227:Lipid Peroxidation; D017270:Lipoprotein(a) / Q000737:chemistry / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014407:Tumor Cells, Cultured
D005609:Free Radicals; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost