Effect of Androgenic and Antiandrogenic Acting Compounds in Macrophage Accumulation and Cell Replication in the Aorta of Oophorectomized Hypercholesterolemic Rabbits

Author(s): Camil Castelo-Branco, Alex Sanjuan, Marta Colodron, Carlos Ascaso, Jaume Ordi, Elena Casals, Juan Balasch, Juan A. Vanrell

Journal Name: Vascular Disease Prevention (Discontinued)

Volume 3 , Issue 4 , 2006


Suppression of cell proliferation and macrophage accumulation by endothelium is believed to play a role in preventing the development of atherosclerosis. We have previously shown that tibolone administration in cholesterol-fed rabbits resulted in reduced extension of lesional areas and that cyproterone acetate induced a greater atheromatosis. Material & Methods: A total of 48 cholesterol-fed New Zealand white rabbits were studied for 4 months. The rabbits were allocated into 6 groups of 8 animals each receiving mixed with the rabbit chow, tibolone (Group T), raloxifene (R), estradiol valerate (E), estradiol valerate plus cyproterone acetate (EC), and no treatment for the control and sham group (C and S). Aorta sections were stained using haematoxylin/eosin (HE) and by an avidin-biotin complex method for smooth muscle cells (SMC) and macrophages (α-actin antibodies and anti-macrophages antibodies RAM 11). For detection of apoptosis and cellular replication BAX and MIB1 antibodies were used. Results: After 12 weeks of atherogenic diet, the extension and thickness of the lesions assessed by HE were greater ingroups C, S, and EC. In these groups, SMC were found in the surface and in the edges, macrophages in the middle and thecells labelled for apoptosis in the deepest lesional zones. In contrast, in groups T and E the lesions showed a more uniformdistribution of macrophages and SMC, nearly without apoptosis and with a smaller degree of replication Conclusion: Tibolone, a compound with androgenic proprieties, may have a preventive action on the genesis of atheromalesions whereas cyproterone acetate an antiandrogenic substance may enhance the progression of atherosclerosis. Theseresults illustrate how difficult it is to predict the effects on atheroma plaque of different drugs based on the characteristicsof the original molecule.

Keywords: Sexual steroids/Estradiol/tibolone/raloxifene/experimental atherosclerosis, α-actin antibodies, RAM 11, apoptosis, BAX, cellular replication, MIB1

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Article Details

Year: 2006
Page: [369 - 374]
Pages: 6
DOI: 10.2174/1567270010603040369
Price: $58