Transfer of Lipoprotein(a) and LDL Into Aortic Intima in Normal and in Cholesterol-Fed Rabbits

Abstract

Abstract To study the relative atherogenic potential of lipoprotein(a) [Lp(a)], the transfer of Lp(a) and LDL into the arterial wall was compared in normal rabbits, cholesterol-fed rabbits, and normal rabbits in which the plasma concentration of Lp(a) before injection of labeled lipoproteins was increased by an intravenous mass injection of 45 mg Lp(a). Aorta was removed either 60 minutes or 180 minutes after intravenous injection of a mixed preparation of human 125 I-Lp(a) and 131 I-LDL; intimal clearance was calculated as radioactivity in aortic intima/inner media divided by the average concentration of the appropriate radioactivity in plasma and by the length of the exposure time. The intimal clearance of labeled Lp(a) and LDL in the aortic arch after 60 minutes of exposure was 87±9 and 47±7 nL · cm −2 · h −1 (n=9) in normal rabbits and 82±14 and 62±10 nL · cm −2 · h −1 (n=10) in cholesterol-fed rabbits; after 180 minutes of exposure, the intimal clearance of labeled Lp(a) and LDL was 62±14 and 84±21 nL · cm −2 · h −1 (n=6) and 30±6 and 47±12 nL · cm −2 · h −1 (n=4) in cholesterol-fed and Lp(a)-injected rabbits, respectively. Linear regression analysis showed positive associations between intimal clearance of the two lipoproteins in all four groups of rabbits in the aortic arch, the thoracic aorta, and the abdominal aorta. Aortic immunoreactivity of human apolipoprotein(a) was detected in the intima in association with fatty streak lesions, predominantly within the cytoplasm of foam cells. These results suggest that Lp(a) is transferred into the aortic intima by a mechanism similar to that for LDL and that Lp(a) can be taken up by intimal foam cells; however, Lp(a) and LDL may be metabolized differently upon entrance into the arterial wall.