on August 29, 2002
Published online before print August 29, 2002, doi: 10.1161/01.ATV.0000035393.11854.6A
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 1, 2002
Accepted on July 19, 2002
Estrogen Regulation of Endothelial and Smooth Muscle Cell Migration and Proliferation. Role of p38 and p42/44 Mitogen-Activated Protein Kinase
Pedro Geraldes ;
From the Department of Medicine (P.G., J.-F.T.), Montreal Heart Institute, and the Department of Pharmacology (M.G.S., P.N.B.), University of Montreal, Montreal, Quebec, Canada.
* To whom correspondence should be addressed. E-mail: tanguay{at}icm.umontreal.ca.
Objective—Restenosis is a major limitation of percutaneous coronary intervention. Migration and proliferation of vascular cells remain a cornerstone in neointimal formation. The cardioprotection of estrogen is well recognized, but the intracellular mechanisms related to these beneficial effects are not completely understood.
Methods and Results—We investigated the effects of 17ß-estradiol (17ßE) on mitogen-activated protein kinase (MAPK) activity and the migration and proliferation of porcine aortic endothelial cells (PAECs) and porcine smooth muscle cells (PSMCs). Treatment with 17ßE (10-8 mol/L) abrogated p38 and p42/44 MAPK phosphorylation mediated by platelet-derived growth factor-BB as well as the migration and proliferation of PSMCs. In contrast, treatment with 17ßE (10-8 mol/L) induced the phosphorylation of p38 and p42/44 MAPK and the migration and proliferation of PAECs. Interestingly, the effects of 17ßE on PSMCs and PAECs were reversed by selective estrogen receptor antagonists (tamoxifen, 4-OH-tamoxifen, and raloxifen). These results suggest that in PSMCs, 17ßE inhibits chemotactic and mitogenic effects of platelet-derived growth factor-BB as well as p38 and p42/44 MAPK phosphorylation. In contrast, 17ßE promotes in PAECs the phosphorylation of p42/44 and p38 MAPK as well as the migration and proliferation of these cells.
Conclusions—Treatment with 17ßE has a dual beneficial effect: the improvement of vascular healing and the prevention of restenosis after angioplasty.
Key words: 17ß-estradiol • smooth muscle • endothelium • mitogen-activated protein kinase
This article has been cited by other articles:
 |
|
 |
|
  C. E. Toutain, C. Filipe, A. Billon, C. Fontaine, L. Brouchet, J.-C. Guery, P. Gourdy, J.-F. Arnal, and F. Lenfant Estrogen Receptor {alpha} Expression in Both Endothelium and Hematopoietic Cells Is Required for the Accelerative Effect of Estradiol on Reendothelialization Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1543 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. N. Armaiz-Pena, L. S. Mangala, W. A. Spannuth, Y. G. Lin, N. B. Jennings, A. M. Nick, R. R. Langley, R. Schmandt, S. K. Lutgendorf, S. W. Cole, et al. Estrous Cycle Modulates Ovarian Carcinoma Growth Clin. Cancer Res., May 1, 2009; 15(9): 2971 - 2978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Filipe, L. Lam Shang Leen, L. Brouchet, A. Billon, V. Benouaich, V. Fontaine, P. Gourdy, F. Lenfant, J.-F. Arnal, A.-P. Gadeau, et al. Estradiol accelerates endothelial healing through the retrograde commitment of uninjured endothelium Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2822 - H2830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Patel and R. R. Arora Review: Endothelial dysfunction: A potential tool in gender related cardiovascular disease Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 89 - 100. [Abstract] [PDF]
|
|
|
|
 |
|
 P. A. Komesaroff Unravelling the Enigma of Dehydroepiandrosterone: Moving Forward Step by Step Endocrinology, March 1, 2008; 149(3): 886 - 888. [Full Text] [PDF]
|
|
|
|
|
|
D. Liu, M. Iruthayanathan, L. L. Homan, Y. Wang, L. Yang, Y. Wang, and J. S. Dillon Dehydroepiandrosterone Stimulates Endothelial Proliferation and Angiogenesis through Extracellular Signal-Regulated Kinase 1/2-Mediated Mechanisms Endocrinology, March 1, 2008; 149(3): 889 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Billon, S. Lehoux, L. Lam Shang Leen, H. Laurell, C. Filipe, V. Benouaich, L. Brouchet, C. Dessy, P. Gourdy, A.-P. Gadeau, et al. The Estrogen Effects on Endothelial Repair and Mitogen-Activated Protein Kinase Activation Are Abolished in Endothelial Nitric-Oxide (NO) Synthase Knockout Mice, but Not by NO Synthase Inhibition by N-Nitro-L-arginine Methyl Ester Am. J. Pathol., March 1, 2008; 172(3): 830 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gentilini, M. Busacca, S. Di Francesco, M. Vignali, P. Vigano, and A.M. Di Blasio PI3K/Akt And ERK1/2 signalling pathways are involved in endometrial cell migration induced by 17{beta}-estradiol and growth factors Mol. Hum. Reprod., May 1, 2007; 13(5): 317 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Fontaine, C. Filipe, N. Werner, P. Gourdy, A. Billon, B. Garmy-Susini, L. Brouchet, F. Bayard, H. Prats, T. Doetschman, et al. Essential Role of Bone Marrow Fibroblast Growth Factor-2 in the Effect of Estradiol on Reendothelialization and Endothelial Progenitor Cell Mobilization Am. J. Pathol., November 1, 2006; 169(5): 1855 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Simoncini, C. Scorticati, P. Mannella, A. Fadiel, M. S. Giretti, X.-D. Fu, C. Baldacci, S. Garibaldi, A. Caruso, L. Fornari, et al. Estrogen Receptor {alpha} Interacts with G{alpha}13 to Drive Actin Remodeling and Endothelial Cell Migration via the RhoA/Rho Kinase/Moesin Pathway Mol. Endocrinol., August 1, 2006; 20(8): 1756 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Geraldes, S. Gagnon, S. Hadjadj, Y. Merhi, M. G. Sirois, I. Cloutier, and J.-F. Tanguay Estradiol blocks the induction of CD40 and CD40L expression on endothelial cells and prevents neutrophil adhesion: An ER{alpha}-mediated pathway Cardiovasc Res, August 1, 2006; 71(3): 566 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Acconcia, C. J. Barnes, and R. Kumar Estrogen and Tamoxifen Induce Cytoskeletal Remodeling and Migration in Endometrial Cancer Cells Endocrinology, March 1, 2006; 147(3): 1203 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kappert, E. Caglayan, M. Huntgeburth, A. T. Baumer, J. Sparwel, M. Uebel, and S. Rosenkranz 17{beta}-Estradiol attenuates PDGF signaling in vascular smooth muscle cells at the postreceptor level Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H538 - H546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.M. Liu, K.W. Choy, W.T. Lui, M.W. Pang, Y.F. Wong, and S.K. Yip 17{beta}-Estradiol suppresses proliferation of fibroblasts derived from cardinal ligaments in patients with or without pelvic organ prolapse Hum. Reprod., January 1, 2006; 21(1): 303 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Costa and D. I. Simon Molecular Basis of Restenosis and Drug-Eluting Stents Circulation, May 3, 2005; 111(17): 2257 - 2273. [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakamura, K. Igarashi, T. Suzuki, J. Kanno, T. Inoue, C. Tazawa, M. Saruta, T. Ando, N. Moriyama, T. Furukawa, et al. E4F1, a Novel Estrogen-Responsive Gene in Possible Atheroprotection, Revealed by Microarray Analysis Am. J. Pathol., December 1, 2004; 165(6): 2019 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Andres Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential Cardiovasc Res, July 1, 2004; 63(1): 11 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Garmy-Susini, E. Delmas, P. Gourdy, M. Zhou, C. Bossard, B. Bugler, F. Bayard, A. Krust, A.C. Prats, T. Doetschman, et al. Role of Fibroblast Growth Factor-2 Isoforms in the Effect of Estradiol on Endothelial Cell Migration and Proliferation Circ. Res., May 28, 2004; 94(10): 1301 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Orshal and R. A. Khalil Gender, sex hormones, and vascular tone Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R233 - R249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Geraldes, M. G. Sirois, and J.-F. Tanguay Specific Contribution of Estrogen Receptors on Mitogen-Activated Protein Kinase Pathways and Vascular Cell Activation Circ. Res., September 5, 2003; 93(5): 399 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Sousa, P. W. Serruys, and M. A. Costa New Frontiers in Cardiology: Drug-Eluting Stents: Part II Circulation, May 13, 2003; 107(18): 2383 - 2389. [Full Text] [PDF]
|
|
|
|
|
|
K. E. Bornfeldt The Cyclin-Dependent Kinase Pathway Moves Forward Circ. Res., March 7, 2003; 92(4): 345 - 347. [Full Text] [PDF]
|
|
|
|
|
|
A. Diez-Juan and V. Andres Coordinate Control of Proliferation and Migration by the p27Kip1/Cyclin-Dependent Kinase/Retinoblastoma Pathway in Vascular Smooth Muscle Cells and Fibroblasts Circ. Res., March 7, 2003; 92(4): 402 - 410. [Abstract] [Full Text] [PDF]
|
|