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

From the Department of Clinical Biochemistry, Rigshospitalet (L.B.N., K.J.), and the Department of Clinical Biochemistry, Herlev Hospital (B.G.N.), University of Copenhagen, Denmark.

Abstract—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 ¹³¹I-TC and ¹²⁵I and injected into 17 rabbits with extensive aortic atherosclerosis and into 16 rabbits without atherosclerosis. As the protein moiety of the doubly labeled lipoproteins is degraded, ¹³¹I-TC is trapped in the cell, whereas ¹²⁵I diffuses out of the cell. Twenty-four hours after injection, 12 samples of the aorta and biopsies from 9 other tissues were removed. The degradation rate of Lp(a) (percent of plasma pool per gram tissue per day) was less than that of LDL in the adrenals and in the intestine. In contrast, degradation rates of Lp(a) and LDL were similar in liver, spleen, kidney, heart, lung, skeletal muscle, 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 aortic 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 compared 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 intima–inner media of the proximal segment of atherosclerotic and nonlesioned aorta, respectively (t test: P <.01). These results suggest that the metabolism of Lp(a) is different from that of LDL in nonlesioned arterial intima, possibly reflecting that Lp(a) is degraded by LDL receptors 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) contributes to foam cell formation during the development of atherosclerosis.

Key Words: atherosclerosis • cholesterol • low-density lipoprotein • macrophages

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