Journal article
Estrogen Replacement Inhibits Intimal Hyperplasia and the Accumulation and Effects of Transforming Growth Factor β1
The Journal of surgical research, Vol.80(2), pp.380-385
12/1998
DOI: 10.1006/jsre.1998.5487
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.
Details
- Title: Subtitle
- Estrogen Replacement Inhibits Intimal Hyperplasia and the Accumulation and Effects of Transforming Growth Factor β1
- Creators
- Craig H. Selzman - University of Colorado HealthJaime S. Gaynor - Colorado State UniversityA.Simon Turner - Colorado State UniversityThomas A. Whitehill - University of Colorado HealthLawrence D. Horwitz - University of Colorado HealthAlden H. Harken - University of Colorado Health
- Resource Type
- Journal article
- Publication Details
- The Journal of surgical research, Vol.80(2), pp.380-385
- Publisher
- Elsevier Inc
- DOI
- 10.1006/jsre.1998.5487
- ISSN
- 0022-4804
- eISSN
- 1095-8673
- Language
- English
- Date published
- 12/1998
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984656602002771
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