Endogenous Estrogen Deficiency Reduces Proliferation and Enhances Apoptosis-Related Death in Vascular Smooth Muscle Cells
- 3 February 2004
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation
- Vol. 109 (4) , 537-543
- https://doi.org/10.1161/01.cir.0000109699.45186.30
Abstract
Background— Altered proliferation and death of vascular smooth muscle cells (VSMCs) are important mechanisms in vascular growth and remodeling. This study examined the effect of endogenous estrogens on VSMC proliferation. Methods and Results— An estrogen-deficient animal model, the aromatase-knockout (ArKO) mouse, was used. Primary cultures of VSMCs were established from aortas of 11-week-old male and female ArKO and wild-type (WT) mice. In ArKO cells, the absence of aromatase cytochrome P450 mRNA expression was demonstrated by reverse transcription–polymerase chain reaction; Western blotting showed normal expression of estrogen receptor protein. Proliferative responses to serum or platelet-derived growth factor-BB were lower in ArKO than WT cells; 17β-estradiol (E2, 10 nmol/L) enhanced the response to platelet-derived growth factor-BB in ArKO cells but inhibited the response in WT cells. E2 inhibited activity of mitogen-activated protein kinase ERK1/2 in WT but not ArKO cells. Apoptosis-related death caused by tumor necrosis factor-α was greater in ArKO than in WT cells; this effect in ArKO was attenuated by E2. Differences in VSMC proliferation between ArKO and WT occurred in both sexes. Morphological studies in aortas derived from male mice at 1 year of age demonstrated that medial smooth muscle area was ≈10% less in ArKO than WT mice at this age. Conclusions— Deficiency of endogenous estrogens reduces proliferation and enhances apoptosis-related death in VSMCs; exogenous E2 corrects these abnormalities.Keywords
This publication has 16 references indexed in Scilit:
- Endogenous Estrogens Influence Endothelial Function in Young MenCirculation Research, 2003
- Meetings of Medical InterestI. Meetings in the United StatesII. International MeetingsPublished by American Medical Association (AMA) ,2002
- Experimental Cardiac Fibrosis: Differential Time Course of Responses to Mineralocorticoid-Salt AdministrationEndocrinology, 2001
- Estrogen inhibits the vascular injury response in estrogen receptor β-deficient female miceProceedings of the National Academy of Sciences, 1999
- Cardiovascular Actions of Estrogens in MenJournal of Clinical Endocrinology & Metabolism, 1999
- Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal WomenJAMA, 1998
- Estrogen and Progesterone Inhibit Vascular Smooth Muscle Proliferation*Endocrinology, 1997
- Effect of Testosterone and Estradiol in a Man with Aromatase DeficiencyNew England Journal of Medicine, 1997
- Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption.Journal of Clinical Investigation, 1997
- Estrogen inhibits the vascular injury response in estrogen receptor α-deficient miceNature Medicine, 1997