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• W2041166938 abstract "Background.The role of estrogens in providing atheroprotection has been well documented in both epidemiologic and experimental studies. This phenomenon has traditionally been attributed to the beneficial lipid-modifying effects of estrogens. Previous studies have used models of either diet- or injury-induced atherosclerosis. As such, the interrelationship between estrogens, lipids, and atherosclerosis remains unclear. We hypothesized that estrogens are atheroprotective independent of changes in serum lipids by directly influencing the accumulation and effects of the peptide growth factor transforming growth factor β1(TGF-β1). Material and methods.Thirteen female sheep (8 years old) were randomized to sham, ovariectomy, or ovariectomy with 17β-estradiol replacement. Serum lipid levels were serially measured. At 9 months, necropsy was performed with histologic morphometric analysis of the aortoiliac bifurcation. Levels of TGF-β1were determined in serum and aortic tissue. Human aortic smooth muscle cells were isolated and cultured. Results.Serum triglyceride, lipoprotein a, and total, low-density lipoprotein, and high-density lipoprotein cholesterol levels were similar and normal between groups. Ovariectomy resulted in aortoiliac intimal hyperplasia compared with sham (P< 0.001) and hormone replacement (P< 0.001) groups. Compared with ovariectomy, estrogen replacement attenuated aortic accumulation of TGF-β1(P< 0.02).In vitro,estradiol potentiated TGF-β1inhibition of human vascular smooth muscle cell (VSMC) proliferation and increased TGF-β1release in stimulated VSMCs (P< 0.001). Conclusions.Without dietary manipulation, ovarian ablation induces aortic intimal hyperplasia in the ewe. Estradiol abrogates this response independently of its effects on serum lipids. Hormone replacement decreases the accumulation of TGF-β1, suggesting that estrogens may provide atheroprotection both by modifying local production and by modulating the influence of TGF-β1on VSMC growth." @default.
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• W2041166938 date "1998-12-01" @default.
• W2041166938 modified "2023-09-25" @default.
• W2041166938 title "Estrogen Replacement Inhibits Intimal Hyperplasia and the Accumulation and Effects of Transforming Growth Factor β1" @default.
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• W2041166938 doi "https://doi.org/10.1006/jsre.1998.5487" @default.
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