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Estrogen suppression of I-125-cholesteryl ester uptake in atherosclerotic lesions in a rabbit model

Conference · · J. Nucl. Med.; (United States)
OSTI ID:6929028
Cholesteryl esters (CE) are the principal lipids found in atherosclerotic lesions. A nonhydrolyzable CE analog, I-125-cholesteryl iopanoate (I-125-CI), that is rapidly associated with circulating lipoproteins was administered to New Zealand White rabbits rendered hypercholesterolemic to assess the effect of hypercholesterolemia and estrogen therapy upon the uptake of CI into developing atherosclerotic lesions. Atherosclerosis (A) was induced by aortic deendothelialization in 10 rabbits with a balloon embolectomy catheter introduced via the femoral artery, followed by a 2% cholesterol-enriched diet. Five of these 10 rabbits were treated with estradiol (AE) (0.5mg/Kg/week x 5); an additional 4 animals served as untreated, non-A controls. I-125-CI was administered intravenously in multiple doses over a 5 week interval. Gamma camera images and selected tissues were obtained 6 days after the completion of I-125-CI administration (total cumulative dose 82.6-87.3..mu..Ci/rabbit). Plasma cholesterol levels were 268 +- 162, 1940 +- 248 and 2484 +- 209 mg/dl in the untreated controls, A and AE groups, respectively. Atherosclerotic aortas were readily visualized in the A > AE groups as compared to untreated controls. Abdominal aortic tissues contained 0.013 +- 0.004, 0.187 +- 0.021, and 0.067 +- 0.015 %-Kg/dose/gm of I-125-CI from the untreated controls, A and AE groups, respectively. Thus, CI analogs can be used as probes to scintigraphically depict CE distribution and the effects of pharmacologic manipulation upon the accumulation of CE by vascular lesions in an animal model of atherosclerosis.
Research Organization:
Univ. of Michigan VA Medical Centers, Ann Arbor, MI 48105
OSTI ID:
6929028
Report Number(s):
CONF-840619-
Conference Information:
Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
Country of Publication:
United States
Language:
English