Transgenic rabbits expressing human apolipoprotein(a) develop more extensive atherosclerotic lesions in response to a cholesterol-rich diet

High lipoprotein(a) [Lp(a)] levels constitute an independent risk factor fo r the development of atherosclerosis, However, the relationship between Lp( a) and atherosclerosis is not fully understood. To examine the effect of Lp (a) on the development of atherosclerosis, we studied transgenic rabbits ex pressing human apolipoprotein(a) [apo(a)], which was assembled into Lp(a) i n the plasma. Human apo(a) transgenic rabbits fed a 0.3% cholesterol diet f or 16 weeks had more extensive atherosclerotic lesions than did nontransgen ic rabbits, although the cholesterol levels in the plasma of both groups we re similarly elevated. Compared with the lesions in control rabbits, the ar eas of the atherosclerotic lesions inhuman apo(a) transgenic rabbits were s ignificantly increased in the aorta, the iliac artery, and the carotid arte ry. Furthermore, human apo(a) transgenic rabbits on a cholesterol-rich diet had a greater degree of coronary atherosclerosis than did control rabbits. Immunohistochemical analysis revealed that human apo(a) was frequently dep osited in the atherosclerotic lesions of transgenic rabbits. We conclude th at Lp(a) may have proatherogenic effects in the setting of a cholesterol-ri ch diet in transgenic rabbits.