LIPOPROTEIN (A) DISPLAYS INCREASED ACCUMULATION COMPARED WITH LOW-DENSITY-LIPOPROTEIN IN THE MURINE ARTERIAL-WALL

Lipoprotein (a) (Lp(a)) is known to be an independent risk factor for cardiovascular disease, but the mechanisms by which it contributes to this disease remain unclear. Current evidence indicates that the close ly related plasma particle, low-density lipoprotein (LDL), may initiat e atherosclerosis through deposition in the arterial wall. This study has compared the ability of both lipoproteins to enter and accumulate within the arterial wall. Experiments were conducted in vivo with anim als from two strains of mice: C57BL/6 mice, which develop fatty streak lesions upon challenge by a high-fat diet, and C3H/HeJ mice, which ar e resistant to lesion formation. Animals from both strains were mainta ined up to 16 weeks either on chow or high-fat diet. The mice were int ravenously injected with I-125-labeled human Lp(a) or I-125-labeled hu man LDL in equimolar amounts and the lipoprotein allowed to circulate in vivo for 2 or 24 h. Transverse sections of the aortic root includin g sites of predilection for lesion formation at the commissures of the valve were prepared and examined after autoradiography. The autoradio graphic grains over lesions and histologically uninvolved areas were e numerated and compared after normalization. Both Lp(a) and LDL demonst rated nearly ten times greater accumulation in lesions compared with h istologically uninvolved areas from C57BL/6 mice; Analyses of histolog ically uninvolved areas from both strains of mice showed a significant ly higher accumulation of Lp(a) than LDL. Finally, significantly highe r accumulations of both Lp(a) and LDL occurred in the histologically u ninvolved intima and subintima of lesion-prone C57BL/6 mice as compare d with lesion-resistant C3H/HeJ mice after 5 weeks on the diets. We pr opose that enhanced accumulation of Lp(a) in the arterial wall account s, in part, for the increased risk of cardiovascular disease.