INCREASED DEGRADATION OF LIPOPROTEIN(A) IN ATHEROSCLEROTIC COMPARED WITH NONLESIONED AORTIC INTIMA-INNER MEDIA OF RABBITS - IN-VIVO EVIDENCE THAT LIPOPROTEIN(A) MAY CONTRIBUTE TO FOAM CELL-FORMATION

To investigate a potential role of lipoprotein(a) [Lp(a)] in foam cell formation, we have measured the degradation rates of Lp(a) and LDL in the rabbit aorta in vivo, Lp(a) (or LDL) was labeled with both I-131- TC and I-125 and injected into 17 rabbits with extensive aortic athero sclerosis and into 16 rabbits without atherosclerosis. As the protein moiety of the doubly labeled lipoproteins is degraded. I-131-TC is tra pped in the cell, whereas I-125 diffuses out of the cell. Twenty-four hours after injection, 12 samples of the aorta and biopsies from 9 oth er tissues were removed. The degradation rate of Lp(a) (percent of pla sma pool per gram tissue per day) was less than that of LDL in the adr enals and in the intestine. In contrast, degradation rates of Lp(a) an d LDL were similar in liver, spleen, kidney, heart, lung, skeletal mus cle, and adipose tissue. In nonlesioned aortic intima-inner media, the degradation rate of Lp(a) was 39% of that of LDL (t test: P <.05 in a ortic arch and thoracic aorta), whereas the degradation rates of Lp(a) and LDL were similar in atherosclerotic aortic intima-inner media. Lp (a) degradation rates were markedly increased in atherosclerotic compa red with nonlesioned aortic intima-inner media: 28.2+/-9.2x10(-7)% and 5.0+/-0.6X10(-7)% of the plasma pool per gram tissue per day in the i ntima-inner media of the proximal segment of atherosclerotic and nonle sioned aorta, respectively (t test: P <.01). These results suggest tha t the metabolism of Lp(a) is different from that of LDL in nonlesioned arterial intima, possibly reflecting that Lp(a) is degraded by LDL re ceptors in arterial intima less efficiently than LDL. The results also indicate that the degradation rate of Lp(a) is markedly increased in atherosclerotic lesions of rabbits, supporting the idea that Lp(a) con tributes to foam cell formation during the development of atherosclero sis.