Arteriosclerosis, Thrombosis, and Vascular Biology. 1990;10:1051-1057
Arteriosclerosis, Vol 10, 1051-1057, Copyright © 1990 by American Heart Association
ARTICLES |
Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone
MR Adams, JR Kaplan, SB Manuck, DR Koritnik, JS Parks, MS Wolfe and TB Clarkson
Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
Although controversy continues, the preponderance of evidence indicates that estrogen replacement therapy favorably influences the risk of coronary heart disease in postmenopausal women. It remains uncertain how this effect is mediated and whether the cyclic addition of a progestin may influence adversely an estrogen-related cardioprotective effect. We investigated the influence of sex hormone replacement therapy on diet-induced coronary artery atherosclerosis in estrogen- deficient (ovariectomized) adult female cynomolgus monkeys. Monkeys were assigned randomly to one of three treatment groups: 1) no hormone replacement (n = 17), 2) continuously administered 17-beta estradiol plus cyclically administered progesterone (n = 20), and 3) continuously administered 17-beta estradiol (n = 18). The physiologic patterns of plasma estradiol and progesterone concentrations were maintained by administering the hormones in sustained-release subcutaneous Silastic implants. The experiment lasted 30 months. At necropsy, coronary artery atherosclerosis was inhibited similarly (reduced by approximately one- half) in animals in both hormone replacement groups (p less than or equal to 0.05). Antiatherogenic effects of hormone replacement were independent of variation in total plasma cholesterol, lipoprotein cholesterol, apoprotein A-1 and B concentrations, high density lipoprotein subfraction heterogeneity, and low density lipoprotein molecular weight. We conclude that physiologic estrogen replacement therapy with or without added progesterone inhibits atherosclerosis progression in ovariectomized monkeys. This may explain why estrogen replacement therapy results in reduced risk of coronary heart disease in postmenopausal women.
This article has been cited by other articles:
 |
|
 |
|
  C. A. Shively, T. C. Register, M. R. Adams, D. L. Golden, S. L. Willard, and T. B. Clarkson Depressive Behavior and Coronary Artery Atherogenesis in Adult Female Cynomolgus Monkeys Psychosom Med, July 1, 2008; 70(6): 637 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-D. Fu, M. Flamini, A. M. Sanchez, L. Goglia, M. S. Giretti, A. R. Genazzani, and T. Simoncini Progestogens regulate endothelial actin cytoskeleton and cell movement via the actin-binding protein moesin Mol. Hum. Reprod., April 1, 2008; 14(4): 225 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Simoncini, X-D. Fu, A. Caruso, S. Garibaldi, C. Baldacci, M.S. Giretti, P. Mannella, M.I. Flamini, A.M. Sanchez, and A.R. Genazzani Drospirenone increases endothelial nitric oxide synthesis via a combined action on progesterone and mineralocorticoid receptors Hum. Reprod., August 1, 2007; 22(8): 2325 - 2334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Seli, O. Guzeloglu-Kayisli, H. Cakmak, U. A. Kayisli, B. Selam, and A. Arici Estradiol Increases Apoptosis in Human Coronary Artery Endothelial Cells by Up-Regulating Fas and Fas Ligand Expression J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4995 - 5001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ouyang, E. D. Michos, and R. H. Karas Hormone Replacement Therapy and the Cardiovascular System: Lessons Learned and Unanswered Questions J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1741 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Clarkson Does tibolone exacerbate atherosclerosis? Eur. Heart J., March 2, 2006; 27(6): 635 - 637. [Full Text] [PDF]
|
|
|
|
 |
|
 U. Hillebrand, M. Hausberg, C. Stock, V. Shahin, D. Nikova, C. Riethmuller, K. Kliche, T. Ludwig, H. Schillers, S.W. Schneider, et al. 17{beta}-estradiol increases volume, apical surface and elasticity of human endothelium mediated by Na+/H+ exchange Cardiovasc Res, March 1, 2006; 69(4): 916 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. Ballard and J. M. Edelberg Harnessing Hormonal Signaling for Cardioprotection Sci. Aging Knowl. Environ., December 21, 2005; 2005(51): re6 - re6. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Elhage, P. Gourdy, J. Jawien, L. Brouchet, C. Castano, C. Fievet, G. K. Hansson, J.-F. Arnal, and F. Bayard The Atheroprotective Effect of 17{beta}-Estradiol Depends on Complex Interactions in Adaptive Immunity Am. J. Pathol., July 1, 2005; 167(1): 267 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Mishra, R. K. Hermsmeyer, K. Miyagawa, P. Sarrel, B. Uchida, F. Z. Stanczyk, K. A. Burry, D. R. Illingworth, and F. J. Nordt Medroxyprogesterone Acetate and Dihydrotestosterone Induce Coronary Hyperreactivity in Intact Male Rhesus Monkeys J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3706 - 3714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Register, J. A. Cann, J. R. Kaplan, J. K. Williams, M. R. Adams, T. M. Morgan, M. S. Anthony, R. M. Blair, J. D. Wagner, and T. B. Clarkson Effects of Soy Isoflavones and Conjugated Equine Estrogens on Inflammatory Markers in Atherosclerotic, Ovariectomized Monkeys J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1734 - 1740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Simoncini, P. Mannella, L. Fornari, A. Caruso, M. Y. Willis, S. Garibaldi, C. Baldacci, and A. R. Genazzani Differential Signal Transduction of Progesterone and Medroxyprogesterone Acetate in Human Endothelial Cells Endocrinology, December 1, 2004; 145(12): 5745 - 5756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Dubey, B. Imthurn, L. C. Zacharia, and E. K. Jackson Hormone Replacement Therapy and Cardiovascular Disease: What Went Wrong and Where Do We Go From Here? Hypertension, December 1, 2004; 44(6): 789 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Adams, J. K. Williams, J. R. Kaplan, K. K. Koh, and I. Sakuma Estrogens, Progestins, and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): e190 - e191. [Full Text] [PDF]
|
|
|
|
|
|
R. K. Bains, S. E. Wells, D. M. Flavell, K. M. Fairhall, M. Strom, P. Le Tissier, and I. C. A. F. Robinson Visceral Obesity without Insulin Resistance in Late-Onset Obesity Rats Endocrinology, June 1, 2004; 145(6): 2666 - 2679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Garbe and S. Suissa Issues to debate on the Women's Health Initiative (WHI) study: Hormone replacement therapy and acute coronary outcomes: methodological issues between randomized and observational studies Hum. Reprod., January 1, 2004; 19(1): 8 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Wagner, D. C. Schwenke, K. A. Greaves, L. Zhang, M. S. Anthony, R. M. Blair, M. K. Shadoan, and J. K. Williams Soy Protein With Isoflavones, but not an Isoflavone-Rich Supplement, Improves Arterial Low-Density Lipoprotein Metabolism and Atherogenesis Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2241 - 2246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Liu, T. B. J. Kuo, and C. C. H. Yang Effects of estrogen on gender-related autonomic differences in humans Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2188 - H2193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakamura, Y. Miki, T. Suzuki, T. Nakata, A. D. Darnel, T. Moriya, C. Tazawa, H. Saito, T. Ishibashi, S. Takahashi, et al. Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta Am. J. Pathol., October 1, 2003; 163(4): 1329 - 1339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Luukkainen Issues to debate on the Women's Health Initiative study: Failure of estrogen plus progestin therapy for prevention of breast cancer risk Hum. Reprod., August 1, 2003; 18(8): 1559 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-S. Lee, C.-W. Liu, S.-H. Juan, Y.-C. Liang, P.-Y. Ho, and Y.-H. Lee Molecular Mechanism of Progesterone-Induced Antiproliferation in Rat Aortic Smooth Muscle Cells Endocrinology, July 1, 2003; 144(7): 2785 - 2790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Antus, P. Hamar, G. Kokeny, Z. Szollosi, I. Mucsi, Z. Nemes, and L. Rosivall Estradiol is nephroprotective in the rat remnant kidney Nephrol. Dial. Transplant., January 1, 2003; 18(1): 54 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. L. Bellino and P. M. Wise Nonhuman Primate Models of Menopause Workshop Biol Reprod, January 1, 2003; 68(1): 10 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Hodgin and N. Maeda Minireview: Estrogen and Mouse Models of Atherosclerosis Endocrinology, December 1, 2002; 143(12): 4495 - 4501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Byington, C. D. Furberg, D. M. Herrington, J. A. Herd, D. Hunninghake, M. Lowery, W. Riley, T. Craven, L. Chaput, C. C. Ireland, et al. Effect of Estrogen Plus Progestin on Progression of Carotid Atherosclerosis in Postmenopausal Women With Heart Disease: HERS B-Mode Substudy Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1692 - 1697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Writing Group for the Women's Health Initiative In Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial JAMA, July 17, 2002; 288(3): 321 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lopez, M. D. Sanchez, W. Shea-Eaton, and M. P. McLean Estrogen Activates the High-Density Lipoprotein Receptor Gene via Binding to Estrogen Response Elements and Interaction with Sterol Regulatory Element Binding Protein-1A Endocrinology, June 1, 2002; 143(6): 2155 - 2168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. McNeill, C. Zhang, F. Z. Stanczyk, S. P. Duckles, and D. N. Krause Estrogen Increases Endothelial Nitric Oxide Synthase via Estrogen Receptors in Rat Cerebral Blood Vessels: Effect Preserved After Concurrent Treatment With Medroxyprogesterone Acetate or Progesterone Stroke, June 1, 2002; 33(6): 1685 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Grady A 60-Year-Old Woman Trying to Discontinue Hormone Replacement Therapy JAMA, April 24, 2002; 287(16): 2130 - 2137. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Darblade, C. Pendaries, A. Krust, S. Dupont, M.-J. Fouque, J. Rami, P. Chambon, F. Bayard, and J.-F. Arnal Estradiol Alters Nitric Oxide Production in the Mouse Aorta Through the {alpha}-, but not {beta}-, Estrogen Receptor Circ. Res., March 8, 2002; 90(4): 413 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Pendaries, B. Darblade, P. Rochaix, A. Krust, P. Chambon, K. S. Korach, F. Bayard, and J.-F. Arnal The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice PNAS, February 19, 2002; 99(4): 2205 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S Mikkola and T. B Clarkson Estrogen replacement therapy, atherosclerosis, and vascular function Cardiovasc Res, February 15, 2002; 53(3): 605 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Amant, P. Holm, S.-h. Xu, N. Tritman, M. Kearney, and D. W. Losordo Estrogen Receptor-Mediated, Nitric Oxide-Dependent Modulation of the Immunologic Barrier Function of the Endothelium: Regulation of Fas Ligand Expression by Estradiol Circulation, November 20, 2001; 104(21): 2576 - 2581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Minshall, D. Pavcnik, P. V. Halushka, and K. Hermsmeyer Progesterone regulation of vascular thromboxane A2 receptors in rhesus monkeys Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1498 - H1507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Grady and S. B. Hulley Postmenopausal hormones and heart disease J. Am. Coll. Cardiol., July 1, 2001; 38(1): 8 - 10. [Full Text] [PDF]
|
|
|
|
|
|
T. Naessen, K. Rodriguez-Macias, and H. Lithell Serum Lipid Profile Improved by Ultra-Low Doses of 17{beta}-Estradiol in Elderly Women J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2757 - 2762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mortensen, V. Breinholt, T. Dalsgaard, H. Frandsen, S. T. Lauridsen, J. Laigaard, B. Ottesen, and J.-J. Larsen 17{beta}-Estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits J. Lipid Res., May 1, 2001; 42(5): 834 - 843. [Abstract] [Full Text]
|
|
|
|
|
|
G.M.C. Rosano, T. Simon, G. Mercuro, S. Sans., K. Schenck-Gustaffson, J.C. Stevenson, E. Swahn, and P. Jaillon Hormone replacement therapy: where we stand in Europe Eur. Heart J., March 2, 2001; 22(6): 439 - 441. [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]
|
|
|
|
 |
|
 S. E. Reis, J. P. Costantino, D. L. Wickerham, E. Tan-Chiu, J. Wang, and M. Kavanah Cardiovascular Effects of Tamoxifen in Women With and Without Heart Disease: Breast Cancer Prevention Trial J Natl Cancer Inst, January 3, 2001; 93(1): 16 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Grady and S. B. Hulley Hormones To Prevent Coronary Disease in Women: When Are Observational Studies Adequate Evidence? Ann Intern Med, December 19, 2000; 133(12): 999 - 1001. [Full Text] [PDF]
|
|
|
|
|
|
G. M. C. Rosano, C. M. Webb, S. Chierchia, G. Luigi Morgani, M. Gabraele, P. M. Sarrel, D. de Ziegler, and P. Collins Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2154 - 2159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Mather, E. G. Norman, J. C. Prior, and T. G. Elliott Preserved Forearm Endothelial Responses with Acute Exposure to Progesterone: A Randomized Cross-Over Trial of 17-{beta} Estradiol, Progesterone, and 17-{beta} Estradiol with Progesterone in Healthy Menopausal Women J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4644 - 4649. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. H. Davidson, K. C. Maki, P. Marx, A. C. Maki, M. S. Cyrowski, N. Nanavati, and J.-C. Arce Effects of Continuous Estrogen and Estrogen-Progestin Replacement Regimens on Cardiovascular Risk Markers in Postmenopausal Women Arch Intern Med, November 27, 2000; 160(21): 3315 - 3325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bausero, M.-H. Ben-Mahdi, J.-P. Mazucatelli, C. Bloy, and M. Perrot-Applanat Vascular endothelial growth factor is modulated in vascular muscle cells by estradiol, tamoxifen, and hypoxia Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2033 - H2042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Herrington, D. M. Reboussin, K. B. Brosnihan, P. C. Sharp, S. A. Shumaker, T. E. Snyder, C. D. Furberg, G. J. Kowalchuk, T. D. Stuckey, W. J. Rogers, et al. Effects of Estrogen Replacement on the Progression of Coronary-Artery Atherosclerosis N. Engl. J. Med., August 24, 2000; 343(8): 522 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rosvall, P. O. Ostergren, B. Hedblad, S-O. Isacsson, L. Janzon, and G. Berglund Occupational Status, Educational Level, and the Prevalence of Carotid Atherosclerosis in a General Population Sample of Middle-aged Swedish Men and Women: Results from the Malmo Diet and Cancer Study Am. J. Epidemiol., August 15, 2000; 152(4): 334 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mosca The Role of Hormone Replacement Therapy in the Prevention of Postmenopausal Heart Disease Arch Intern Med, August 14, 2000; 160(15): 2263 - 2272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Simoncini, S. Maffei, G. Basta, G. Barsacchi, A. R. Genazzani, J. K. Liao, and R. De Caterina Estrogens and Glucocorticoids Inhibit Endothelial Vascular Cell Adhesion Molecule-1 Expression by Different Transcriptional Mechanisms Circ. Res., July 7, 2000; 87(1): 19 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hayashi, M. Jayachandran, D. Sumi, N. K. Thakur, T. Esaki, E. Muto, H. Kano, Y. Asai, and A. Iguchi Physiological Concentration of 17{beta}-Estradiol Retards the Progression of Severe Atherosclerosis Induced by a High-Cholesterol Diet Plus Balloon Catheter Injury : Role of NO Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1613 - 1621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nakagomi, S. B. Freedman, and C. L. Geczy Interferon-{gamma} and Lipopolysaccharide Potentiate Monocyte Tissue Factor Induction by C-Reactive Protein : Relationship With Age, Sex, and Hormone Replacement Treatment Circulation, April 18, 2000; 101(15): 1785 - 1791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi, I. Ito, H. Kano, H. Endo, and A. Iguchi Estriol (E3) Replacement Improves Endothelial Function and Bone Mineral Density in Very Elderly Women J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2000; 55(4): 183B - 190. [Abstract] [Full Text]
|
|
|
|
|
|
T. Hayashi, T. Esaki, E. Muto, H. Kano, Y. Asai, N. K. Thakur, D. Sumi, M. Jayachandran, and A. Iguchi Dehydroepiandrosterone Retards Atherosclerosis Formation Through Its Conversion to Estrogen : The Possible Role of Nitric Oxide Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 782 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Peterson, M. Courtois, L. F. Peterson, M. R. Peterson, V. G. Dávila-Román, R. J. Spina, and B. Barzilai Estrogen Increases Hyperemic Microvascular Blood Flow Velocity in Postmenopausal Women J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2000; 55(3): 174M - 179. [Abstract] [Full Text]
|
|
|
|
|
|
R. H. Karas, J. B. Hodgin, M. Kwoun, J. H. Krege, M. Aronovitz, W. Mackey, J. A. Gustafsson, K. S. Korach, O. Smithies, and M. E. Mendelsohn Estrogen inhibits the vascular injury response in estrogen receptor beta -deficient female mice PNAS, December 21, 1999; 96(26): 15133 - 15136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhu, B. Bonet, H. Gillenwater, and R. H. Knopp Opposing Effects of Estrogen and Progestins on LDL Oxidation and Vascular Wall Cytotoxicity: Implications for Atherogenesis Experimental Biology and Medicine, December 1, 1999; 222(3): 214 - 221. [Abstract] [Full Text]
|
|
|
|
|
|
I. C. D. Westendorp, B. A. I.’t Veld, M. L. Bots, J. M. Akkerhuis, A. Hofman, D. E. Grobbee, and J. C. M. Witteman Hormone Replacement Therapy and Intima-Media Thickness of the |