This Article Full Text Full Text (PDF) Data Supplement Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Hayashi, T. Articles by Iguchi, A. Search for Related Content PubMed PubMed Citation Articles by Hayashi, T. Articles by Iguchi, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL ESTRADIOL NITRIC OXIDE Medline Plus Health Information Dietary Fats Related Collections Cardiovascular Pharmacology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1613.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Physiological Concentration of 17ß-Estradiol Retards the Progression of Severe Atherosclerosis Induced by a High-Cholesterol Diet Plus Balloon Catheter Injury

Role of NO

Toshio Hayashi; Muthuvel Jayachandran; Daigo Sumi; Navin Kumar Thakur; Teiji Esaki; Emiko Muto; Hatsuyo Kano; Yukako Asai; Akihisa Iguchi

From the Department of Geriatrics, Nagoya University School of Medicine, Nagoya, Japan.

Correspondence to Toshio Hayashi, MD, Department of Geriatrics, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466, Japan. E-mail hayashi{at}med.nagoya-u.ac.jp

Abstract—The molecular mechanisms of the antiatherosclerotic effects of estrogen are not yet known. We evaluated the effects of 17ß-estradiol (E₂) on high cholesterol diet– (HCD; standard diet and 1% cholesterol) and balloon injury–induced atherosclerosis in female New Zealand White rabbits. The abdominal aortas of 40 oophorectomized (Groups 1 through 5) and 8 nonoophorectomized (Group 6) rabbits were injured by balloon catheter, and the animals were then divided into the following groups and treated for 10 weeks: Group 1, standard diet; Group 2, standard diet plus a moderate dose of E₂ (100 µg · kg^-1 · d^-1); Group 3, HCD; Group 4, HCD plus a moderate dose of E₂; Group 5, HCD plus a low dose of E₂ (20 µg · kg^-1 · d^-1); and Group 6, HCD in nonoophorectomized rabbits. After the treatment phase, plasma E₂ was increased up to 282.2±45.5 pg/mL in Group 2, 263.0±41.5 pg/mL in Group 4, 87.9±18.8 pg/mL in Group 5, and 45.6±7.3 pg/mL in Group 6. HCD-mediated increases in plasma lipid levels were not changed by E₂ treatment, whereas E₂ decreased the aortic intimal thickening in Group 2 animals compared with those in Group 1 and reduced atherosclerosis in the thoracic and abdominal aortas of Group 4, 5, and 6 rabbits compared with those in Group 3. E₂ restored the impaired abdominal aortic endothelium–dependent relaxation of balloon-injured and HCD-supplemented rabbits, and E₂ increased basal nitric oxide (NO) release. The basal NO–releasing effect showed a significant, inverse relation with the severity of atherosclerosis. Plasma E₂ concentration also showed a significant, inverse relation with atherosclerotic area. In conclusion, physiological concentrations of E₂ can retard the progression of severe atherosclerosis and stabilize atheromas induced by HCD and balloon injury. The retardation may be partially mediated by endothelial NO function in vessels treated with E₂.

Key Words: nitric oxide • estradiol • arteriosclerosis • balloon injury • endothelium

This article has been cited by other articles:

				A. Farsetti, A. Grasselli, S. Bacchetti, C. Gaetano, and M. C. Capogrossi The telomerase tale in vascular aging: regulation by estrogens and nitric oxide signaling J Appl Physiol, January 1, 2009; 106(1): 333 - 337. [Abstract] [Full Text] [PDF]

				A. Miyazaki-Akita, T. Hayashi, Q. F. Ding, H. Shiraishi, T. Nomura, Y. Hattori, and A. Iguchi 17beta-Estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase I by High Glucose: Relevance to Postmenopausal Diabetic Cardiovascular Disease J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 591 - 598. [Abstract] [Full Text] [PDF]

				T. Hayashi, H. Matsui-Hirai, A. Miyazaki-Akita, A. Fukatsu, J. Funami, Q.-F. Ding, S. Kamalanathan, Y. Hattori, L. J. Ignarro, and A. Iguchi Endothelial cellular senescence is inhibited by nitric oxide: Implications in atherosclerosis associated with menopause and diabetes PNAS, November 7, 2006; 103(45): 17018 - 17023. [Abstract] [Full Text] [PDF]

				T. Hayashi, T. Esaki, D. Sumi, T. Mukherjee, A. Iguchi, and G. Chaudhuri Modulating role of estradiol on arginase II expression in hyperlipidemic rabbits as an atheroprotective mechanism PNAS, July 5, 2006; 103(27): 10485 - 10490. [Abstract] [Full Text] [PDF]

				B. J. Wu, K. Kathir, P. K. Witting, K. Beck, K. Choy, C. Li, K. D. Croft, T. A. Mori, D. Tanous, M. R. Adams, et al. Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging J. Exp. Med., April 17, 2006; 203(4): 1117 - 1127. [Abstract] [Full Text] [PDF]

				A. L. Chancey, J. D. Gardner, D. B. Murray, G. L. Brower, and J. S. Janicki Modulation of cardiac mast cell-mediated extracellular matrix degradation by estrogen Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H316 - H321. [Abstract] [Full Text] [PDF]

				T. Hayashi, D. Sumi, P. A.R Juliet, H. Matsui-Hirai, Y. Asai-Tanaka, H. Kano, A. Fukatsu, T. Tsunekawa, A. Miyazaki, A. Iguchi, et al. Gene transfer of endothelial NO synthase, but not eNOS, plus inducible NOS regressed atherosclerosis in rabbits Cardiovasc Res, February 1, 2004; 61(2): 339 - 351. [Abstract] [Full Text] [PDF]

				M. Jayachandran and V. M. Miller Ovariectomy upregulates expression of estrogen receptors, NOS, and HSPs in porcine platelets Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H220 - H226. [Abstract] [Full Text] [PDF]