Tamoxifen elevates transforming growth factor–β and suppresses diet–induced formation of lipid lesions in mouse aorta

Abstract
When CS7BI6 male mice are fed a high–fat diet, they develop significant 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 body weight per day, suppressed the diet–induced increase in the area of lipid staining in the aortic sinus of the mice by 88% and in the average number of lesions by 86%. The TMX–treated mice had 11% ± 5% less total plasma cholesterol, with most of the reduction in the high density lipoprotein fraction, whereas plasma triglycerides were significantly elevated, and circulating concentrations of 17β–estradiol and testosterone were unaffected. Both circulating and aortic concentrations of active and latent transforming growth factor–β (TGF–β) were substantially elevated by TMX. The inhibition of lesion formation may be due, at least in part, to cardiovascular protection by TGF–β.

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