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 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 17 beta-estradiol and testosterone were unaffected. Both circulating and aortic concentrations of active and latent transforming growth factor-beta (TGF-beta) were substantially elevated by TMX. The inhibition of lesion formation may be due, at least in part, to cardiovascular protection by TGF-beta.
D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004958:Estradiol / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000819:agonists* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D000199:Actins; D004041:Dietary Fats; D012739:Gonadal Steroid Hormones; D008074:Lipoproteins; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D013629:Tamoxifen; D053495:Osteopontin; D013739:Testosterone; D004958:Estradiol; D002784:Cholesterol