Modulating role of estradiol on arginase II expression in hyperlipidemic rabbits as an atheroprotective mechanism.
We evaluated the effects of a 0.5% cholesterol-enriched diet (HCD) on nitric-oxide synthase (NOS) and arginase expression and the modulating role of 17beta-estradiol (E(2)) on this phenomenon. Thirty oopherectomized rabbits were divided into three groups and treated for 15 weeks. Group I received normal chow; group II, HCD; and group III, HCD plus E(2) pellets. Animals in group II showed an increase in plasma lipids, and they demonstrated atheromatous lesions as well as expression of arginase I and II accompanied by a significant number of BrdU-positive cells in endothelial cells and intimal muscle cells, suggestive of an increase in cellular proliferation. There was significant expression of inducible NOS and increased staining of nitrotyrosine-positive areas. These were not observed in group I animals. In both groups, E(2) levels were low. In group III animals, E(2) supplementation led to a decrease in atheromatous lesions and BrdU-positive cells and reduced expression of both inducible NOS and arginase I and II accompanied by a decrease in nitrotyrosine staining. E(2) levels were increased. Our results suggest that E(2) was responsible for these effects, despite the animals being hyperlipidemic, similar to those in group II. Because arginase is responsible for cell proliferation by converting l-arginine to polyamines, our results indicate that expression of arginase may play an important role in cellular proliferation in atherosclerosis, and inhibition of arginase expression by E(2) may be another potential mechanism in attenuating atherogenesis.
Hayashi
Toshio
T
*Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan; hayashi@med.nagoya-u.ac.jp.
Esaki
Teiji
T
*Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.|Department of Geriatrics, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, 396 Yatomi-town, Ama-gun, Aichi Prefecture 498-8502, Japan; and.
Sumi
Daigo
D
Department of Obstetrics and Gynecology and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, 650 Charles E. Young Drive South, University of California, Los Angeles, CA 90095-1735.
Mukherjee
Tapan
T
Department of Obstetrics and Gynecology and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, 650 Charles E. Young Drive South, University of California, Los Angeles, CA 90095-1735.
Iguchi
Akihisa
A
*Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Chaudhuri
Gautam
G
Department of Obstetrics and Gynecology and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, 650 Charles E. Young Drive South, University of California, Los Angeles, CA 90095-1735.
D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement; D004195:Disease Models, Animal; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011817:Rabbits; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D008055:Lipids; C002744:3-nitrotyrosine; D014443:Tyrosine; D004958:Estradiol; D052247:Nitric Oxide Synthase Type II; D001119:Arginase; D001973:Bromodeoxyuridine