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 wh ether native and oxidized lipoprotein(a) (Lp(a)) can induce adhesion o f monocytic cells to aortic endothelium. The extensive oxidation of pa ired samples of Lp(a) and low-density lipoprotein (LDL) was achieved b y O-2(.-)/OH. free radicals produced by gamma radiolysis of water, lea ding to similar values for the formation of peroxidation markers (conj ugated dienes, TBARS, 8-epi-PGF2 alpha) for both Lp(a) and LDL. Rabbit aortic segments were incubated for 5 h in the presence of equimolar c oncentrations of native and oxidized preparations of Lp(a) and LDL (12 5 mu mol cholesterol/1, corresponding to 40 and 30 mg protein/1 for Lp (a) and LDL, respectively). The aortic segments were incubated with rh odamin-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 a dhesion 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 nati ve 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 propert ies of the arterial endothelium which may account for its proatherogen ic action. Furthermore, our results show that oxidized Lp(a), as well as oxidized LDL, are potent stimuli of monocyte adhesion to endothelia l cells. (C) 1997 Elsevier Science Ireland Ltd.