TAMOXIFEN ELEVATES TRANSFORMING GROWTH-FACTOR-BETA AND SUPPRESSES DIET-INDUCED FORMATION OF LIPID LESIONS IN MOUSE AORTA

When C57B16 male mice are fed a high-fat diet, they develop significan t fatty streak lesions in the aorta. Addition of tamoxifen (TMX) to a high-fat diet, equivalent to a dose of approximately 1 mg TMX per kg b ody weight per day, suppressed the diet-induced increase in the area o f lipid staining in the aortic sinus of the mice by 88% and in the ave rage number of lesions by 86%. The TMX-treated mice had 11% +/- 5% les s total plasma cholesterol, with most of the reduction in the high den sity lipoprotein fraction, whereas plasma triglycerides were significa ntly elevated, and circulating concentrations of 17 beta-estradiol and testosterone were unaffected. Both circulating and aortic concentrati ons of active and latent transforming growth factor-beta (TGF-beta) we re substantially elevated by TMX. The inhibition of lesion formation m ay be due, at least in part, to cardiovascular protection by TGF-beta.