This Article Full Text Full Text (PDF) 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, G. Articles by Thompson, J. A. Search for Related Content PubMed PubMed Citation Articles by Li, G. Articles by Thompson, J. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL TEFLON Related Collections Animal models of human disease Smooth muscle proliferation and differentiation Receptor pharmacology

(Circulation. 1999;100:1639-1645.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Estrogen Inhibits Vascular Smooth Muscle Cell–Dependent Adventitial Fibroblast Migration In Vitro

Guohong Li, MD, PhD; Yiu-Fai Chen, PhD; Geoffrey L. Greene, PhD; Suzanne Oparil, MD; John A. Thompson, PhD

From the University of Alabama at Birmingham, Departments of Medicine, Vascular Biology and Hypertension Program, and Surgery, Division of Transplantation; and the Ben May Institute for Cancer Research, University of Chicago (G.L.G.), Chicago, Ill.

Correspondence to John A. Thompson, PhD, 752 Lyons Harrison Research Bldg, 701 S 19th St, Birmingham, AL 35294-0007. E-mail athompson{at}ms.surgery.uab.edu

Background—Mounting experimental evidence suggests that estrogen treatment protects against neointima formation in response to vascular injury in vivo. Previous studies have suggested that this process includes the activation and migration of adventitial fibroblasts. The present in vitro study was designed to establish a mechanism whereby estrogen attenuates migration of adventitial fibroblasts.

Methods and Results—Primary cultures of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts were derived from female Sprague-Dawley rats. Reverse transcriptase–polymerase chain reaction and Western blotting were used to determine that expression of the estrogen receptor (ER) was restricted to early-passage VSMCs. Migration of transduced (retrovirally mediated) fibroblasts was determined by counting the number of blue lacZ-expressing cells attached to Boyden-type chambers preconditioned under defined experimental conditions. Compared with growth medium alone, chambers treated with medium conditioned by VSMCs demonstrated a 2-fold increase in fibroblast migration, suggesting that VSMCs release soluble factor(s) competent to bind the Transwell membrane and promote fibroblast migration. In contrast, treatment of VSMCs with 17ß-estradiol (10^-9 to 10^-7 mol/L) before preconditioning of the chamber induced a dose-dependent inhibition of fibroblast migration. Cotreatment of VSMCs with 17ß-estradiol and the ER antagonist ICI-182780 (10^-7 mol/L) blocked the inhibitory effect of estrogen on fibroblast migration.

Conclusions—These observations suggest a novel mechanism of hormonal vasoprotection by which estrogen directly modulates VSMC expression of factor(s) controlling migration of adventitial fibroblasts via an ER-dependent mechanism.

Key Words: hormones • cells • muscle, smooth • arteries • restenosis

This article has been cited by other articles:

				R. Marfella, C. Di Filippo, M. Portoghese, F. Ferraraccio, B. Crescenzi, M. Siniscalchi, M. Barbieri, C. Bologna, M. R. Rizzo, F. Rossi, et al. Proteasome Activity as a Target of Hormone Replacement Therapy-Dependent Plaque Stabilization in Postmenopausal Women Hypertension, April 1, 2008; 51(4): 1135 - 1141. [Abstract] [Full Text] [PDF]

				D. Xing, W. Feng, A. P. Miller, N. M. Weathington, Y.-F. Chen, L. Novak, J. E. Blalock, and S. Oparil Estrogen modulates TNF-{alpha}-induced inflammatory responses in rat aortic smooth muscle cells through estrogen receptor-beta activation Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2607 - H2612. [Abstract] [Full Text] [PDF]

				J.-M. Li, M. Iwai, T.-X. Cui, L.-J. Min, M. Tsuda, J. Iwanami, J. Suzuki, M. Mogi, and M. Horiuchi Effect of Azelnidipine on Angiotensin II-Mediated Growth-Promoting Signaling in Vascular Smooth Muscle Cells Mol. Pharmacol., May 1, 2005; 67(5): 1666 - 1673. [Abstract] [Full Text] [PDF]

				D. Xing, A. Miller, L. Novak, R. Rocha, Y.-F. Chen, and S. Oparil Estradiol and Progestins Differentially Modulate Leukocyte Infiltration After Vascular Injury Circulation, January 20, 2004; 109(2): 234 - 241. [Abstract] [Full Text] [PDF]

				J.-M. Li, T.-X. Cui, T. Shiuchi, H.-W. Liu, L.-J. Min, M. Okumura, T. Jinno, L. Wu, M. Iwai, and M. Horiuchi Nicotine Enhances Angiotensin II-Induced Mitogenic Response in Vascular Smooth Muscle Cells and Fibroblasts Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 80 - 84. [Abstract] [Full Text] [PDF]

				J. Titze, R. Lang, C. Ilies, K. H. Schwind, K. A. Kirsch, P. Dietsch, F. C. Luft, and K. F. Hilgers Osmotically inactive skin Na+ storage in rats Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1108 - F1117. [Abstract] [Full Text]

				A. P. Miller, Y.-F. Chen, D. Xing, W. Feng, and S. Oparil Hormone Replacement Therapy and Inflammation: Interactions in Cardiovascular Disease Hypertension, October 1, 2003; 42(4): 657 - 663. [Abstract] [Full Text] [PDF]

				F. E. Rey and P. J. Pagano The Reactive Adventitia: Fibroblast Oxidase in Vascular Function Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 1962 - 1971. [Abstract] [Full Text] [PDF]

				R. K. Dubey, S. Oparil, B. Imthurn, and E. K. Jackson Sex hormones and hypertension Cardiovasc Res, February 15, 2002; 53(3): 688 - 708. [Abstract] [Full Text] [PDF]

				S. Sartore, A. Chiavegato, E. Faggin, R. Franch, M. Puato, S. Ausoni, and P. Pauletto Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling: From Innocent Bystander to Active Participant Circ. Res., December 7, 2001; 89(12): 1111 - 1121. [Abstract] [Full Text] [PDF]

				R. K. Dubey and E. K. Jackson Genome and Hormones: Gender Differences in Physiology: Invited Review: Cardiovascular protective effects of 17{beta}-estradiol metabolites J Appl Physiol, October 1, 2001; 91(4): 1868 - 1883. [Abstract] [Full Text] [PDF]

				R. K. Dubey and E. K. Jackson Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388. [Abstract] [Full Text] [PDF]

				V. M. Miller Vascular Control During Pregnancy : Extending Experimental Findings to Humans Circ. Res., September 1, 2000; 87(5): 344 - 345. [Full Text] [PDF]

				G. Li, Y.-F. Chen, S. S. Kelpke, S. Oparil, and J. A. Thompson Estrogen Attenuates Integrin-{beta}3-Dependent Adventitial Fibroblast Migration After Inhibition of Osteopontin Production in Vascular Smooth Muscle Cells Circulation, June 27, 2000; 101(25): 2949 - 2955. [Abstract] [Full Text] [PDF]

				G. Li, S.-J. Chen, S. Oparil, Y.-F. Chen, and J. A. Thompson Direct In Vivo Evidence Demonstrating Neointimal Migration of Adventitial Fibroblasts After Balloon Injury of Rat Carotid Arteries Circulation, March 28, 2000; 101(12): 1362 - 1365. [Abstract] [Full Text] [PDF]

				S. Oparil, S.-J. Chen, Y.-F. Chen, J. N Durand, L. Allen, and J. A Thompson Estrogen attenuates the adventitial contribution to neointima formation in injured rat carotid arteries Cardiovasc Res, December 1, 1999; 44(3): 608 - 614. [Abstract] [Full Text] [PDF]

				K. J. Scheidegger, B. Cenni, D. Picard, and P. Delafontaine Estradiol Decreases IGF-1 and IGF-1 Receptor Expression in Rat Aortic Smooth Muscle Cells. MECHANISMS FOR ITS ATHEROPROTECTIVE EFFECTS J. Biol. Chem., December 1, 2000; 275(49): 38921 - 38928. [Abstract] [Full Text] [PDF]