This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by O’Lone, R. Articles by Hansen, U. Search for Related Content PubMed PubMed Citation Articles by O’Lone, R. Articles by Hansen, U.

Estrogen Receptors and ß Mediate Distinct Pathways of Vascular Gene Expression, Including Genes Involved in Mitochondrial Electron Transport and Generation of Reactive Oxygen Species

Department of Biology (R.O., U.H.), Program in Bioinformatics (M.E.S., U.H.), and Department of Biomedical Engineering (J.B.), Boston University, Boston, Massachusetts 02215; Molecular Cardiology Research Institute (K.K., I.Z.J., R.H.K., M.E.M.), Tufts-New England Medical Center, Boston, Massachusetts 02111; CSAIL (J.B.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; and Institute of Endocrinology (P.G.V.M.), University of Milan, 20133 Milan, Italy

Address all correspondence and requests for reprints to: Dr. Ulla Hansen, 5 Cummington Street, Boston Massachusetts 02215. E-mail: uhansen{at}bu.edu.

Estrogen plays an important role in the regulation of vascular tone and in the pathophysiology of cardiovascular disease. Physiological effects of estrogen are mediated through estrogen receptors (ER) and ß (ERß), which are both expressed in vascular smooth muscle and endothelial cells. However, the molecular pathways mediating estrogen effects in blood vessels are not well defined. We have performed gene expression profiling in the mouse aorta to identify comprehensive gene sets the expression of which is regulated by long-term (1 wk) estrogen treatment. The ER subtype dependence of the alterations in gene expression was characterized by parallel gene expression profiling experiments in ER-deficient [ER knockout (ERKO)] and ERß-deficient (ERßKO) mice. Importantly, these data revealed that ER- and ERß-dependent pathways regulate distinct and largely nonoverlapping sets of genes. Whereas ER is essential for most of the estrogen-mediated increase in gene expression in wild-type aortas, ERß mediates the large majority (nearly 90%) of estrogen-mediated decreases in gene expression. Biological functions of the estrogen-regulated genes include extracellular matrix synthesis, in addition to electron transport in the mitochondrion and reactive oxygen species pathways. Of note, the estrogen/ERß pathway mediates down-regulation of mRNAs for nuclear-encoded subunits in each of the major complexes of the mitochondrial respiratory chain. Several estrogen-regulated genes also encode transcription factors. Computational analysis of promoters from coexpressed genes revealed overrepresentation of binding sites for such factors, lending support for an estrogen-regulatory transcriptional network in the vasculature. Overall, these findings provide a foundation for understanding the molecular basis for estrogen effects on vasculature gene expression.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα  |  ERβ

Ligands:   17β-Estradiol

This article has been cited by other articles:

				M. R. Meyer and M. Barton ER{alpha}, ER{beta}, and gpER: novel aspects of oestrogen receptor signalling in atherosclerosis Cardiovasc Res, September 1, 2009; 83(4): 605 - 610. [Full Text] [PDF]

				K. E. Roberts, M. B. Fallon, M. J. Krowka, R. S. Brown, J. F. Trotter, I. Peter, H. Tighiouart, J. A. Knowles, D. Rabinowitz, R. L. Benza, et al. Genetic Risk Factors for Portopulmonary Hypertension in Patients with Advanced Liver Disease Am. J. Respir. Crit. Care Med., May 1, 2009; 179(9): 835 - 842. [Abstract] [Full Text] [PDF]

				S.-H. Yang, S. N. Sarkar, R. Liu, E. J. Perez, X. Wang, Y. Wen, L.-J. Yan, and J. W. Simpkins Estrogen Receptor {beta} as a Mitochondrial Vulnerability Factor J. Biol. Chem., April 3, 2009; 284(14): 9540 - 9548. [Abstract] [Full Text] [PDF]

				A. Cignarella, C. Bolego, V. Pelosi, C. Meda, A. Krust, C. Pinna, R. M. Gaion, E. Vegeto, and A. Maggi Distinct Roles of Estrogen Receptor-{alpha} and {beta} in the Modulation of Vascular Inducible Nitric-Oxide Synthase in Diabetes J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 174 - 182. [Abstract] [Full Text] [PDF]

				G. W. Aberdeen, S. J. Wiegand, T. W. Bonagura Jr., G. J. Pepe, and E. D. Albrecht Vascular Endothelial Growth Factor Mediates the Estrogen-Induced Breakdown of Tight Junctions between and Increase in Proliferation of Microvessel Endothelial Cells in the Baboon Endometrium Endocrinology, December 1, 2008; 149(12): 6076 - 6083. [Abstract] [Full Text] [PDF]

				S. Tsutsumi, X. Zhang, K. Takata, K. Takahashi, R. H Karas, H. Kurachi, and M. E Mendelsohn Differential regulation of the inducible nitric oxide synthase gene by estrogen receptors 1 and 2 J. Endocrinol., November 1, 2008; 199(2): 267 - 273. [Abstract] [Full Text] [PDF]

				K. K. Schnoes, I. Z. Jaffe, L. Iyer, A. Dabreo, M. Aronovitz, B. Newfell, U. Hansen, G. Rosano, and M. E. Mendelsohn Research Resource: Rapid Recruitment of Temporally Distinct Vascular Gene Sets by Estrogen Mol. Endocrinol., November 1, 2008; 22(11): 2544 - 2556. [Abstract] [Full Text] [PDF]

				C. M. Klinge, N. S. Wickramasinghe, M. M. Ivanova, and S. M. Dougherty Resveratrol stimulates nitric oxide production by increasing estrogen receptor {alpha}-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells FASEB J, July 1, 2008; 22(7): 2185 - 2197. [Abstract] [Full Text] [PDF]

				V. M. Miller and S. P. Duckles Vascular Actions of Estrogens: Functional Implications Pharmacol. Rev., June 1, 2008; 60(2): 210 - 241. [Abstract] [Full Text] [PDF]

				K. A. Mattingly, M. M. Ivanova, K. A. Riggs, N. S. Wickramasinghe, M. J. Barch, and C. M. Klinge Estradiol Stimulates Transcription of Nuclear Respiratory Factor-1 and Increases Mitochondrial Biogenesis Mol. Endocrinol., March 1, 2008; 22(3): 609 - 622. [Abstract] [Full Text] [PDF]

				S. E. Hook, A. D. Skillman, B. Gopalan, J. A. Small, and I. R. Schultz Gene Expression Profiles in Rainbow Trout, Onchorynchus mykiss, Exposed to a Simple Chemical Mixture Toxicol. Sci., March 1, 2008; 102(1): 42 - 60. [Abstract] [Full Text] [PDF]