Circulation. 2002;106:2767-2770
Published online before print November 4, 2002, doi: 10.1161/01.CIR.0000042707.50032.19
Published online before print November 4, 2002, doi: 10.1161/01.CIR.0000042707.50032.19
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(Circulation. 2002;106:2767.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice
From the Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan (Y.O., S.K., N.O., M.N., Y.A., M.K., K.O., N.S., I.S., T.F., Y.M.); and Sankyo Co, Ltd, Shinagawa-ku, Tokyo, Japan (H.K., N.T., T.I.).
Correspondence to Shinji Kihara, Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 B5 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail kihara{at}imed2.med.osaka-u.ac.jp
Background— Dysregulation of adipocyte-derived bioactive molecules plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the injured artery from the plasma and suppressed endothelial inflammatory response and vascular smooth muscle cell proliferation, as well as macrophage-to-foam cell transformation in vitro. The current study investigated whether the increased plasma adiponectin could actually reduce atherosclerosis in vivo.
Methods and Results— Apolipoprotein E-deficient mice were treated with recombinant adenovirus expressing human adiponectin (Ad-APN) or ß-galactosidase (Ad-ßgal). The plasma adiponectin levels in Ad-APN–treated mice increased 48 times as much as those in Ad-ßgal treated mice. On the 14th day after injection, the lesion formation in aortic sinus was inhibited in Ad-APN–treated mice by 30% compared with Ad-ßgal–treated mice (P<0.05). In the lesions of Ad-APN–treated mice, the lipid droplets became smaller compared with Ad-ßgal–treated mice (P<0.01). Immunohistochemical analyses demonstrated that the adenovirus-mediated adiponectin migrate to foam cells in the fatty streak lesions. The real-time quantitative polymerase chain reaction revealed that Ad-APN treatment significantly suppressed the mRNA levels of vascular cell adhesion molecule-1 by 29% and class A scavenger receptor by 34%, and tended to reduce levels of tumor necrosis factor-
without affecting those of CD36 in the aortic tissue.
Conclusions— These findings documented for the first time that elevated plasma adiponectin suppresses the development of atherosclerosis in vivo.
Key Words: proteins • atherosclerosis • plasma • remodeling
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C. G. Schalkwijk, N. Chaturvedi, M. T. Schram, J. H. Fuller, C. D. A. Stehouwer, and the EURODIAB Prospective Complications Study Group Adiponectin Is Inversely Associated with Renal Function in Type 1 Diabetic Patients J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 129 - 135. [Abstract] [Full Text] [PDF]
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H. Kato, H. Kashiwagi, M. Shiraga, S. Tadokoro, T. Kamae, H. Ujiie, S. Honda, S. Miyata, Y. Ijiri, J. Yamamoto, et al. Adiponectin Acts as an Endogenous Antithrombotic Factor Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 224 - 230. [Abstract] [Full Text] [PDF]
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 B. Iglseder, V. Mackevics, A. Stadlmayer, G. Tasch, G. Ladurner, and B. Paulweber Plasma Adiponectin Levels and Sonographic Phenotypes of Subclinical Carotid Artery Atherosclerosis: Data From the SAPHIR Study Stroke, December 1, 2005; 36(12): 2577 - 2582. [Abstract] [Full Text] [PDF]
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C. Kistorp, J. Faber, S. Galatius, F. Gustafsson, J. Frystyk, A. Flyvbjerg, and P. Hildebrandt Plasma Adiponectin, Body Mass Index, and Mortality in Patients With Chronic Heart Failure Circulation, September 20, 2005; 112(12): 1756 - 1762. [Abstract] [Full Text] [PDF]
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P. W Peake, A. D Kriketos, L. V Campbell, Y. Shen, and J. A Charlesworth The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals Eur. J. Endocrinol., September 1, 2005; 153(3): 409 - 417. [Abstract] [Full Text] [PDF]
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A. Singhal, N. Jamieson, M. Fewtrell, J. Deanfield, A. Lucas, and N. Sattar Adiponectin Predicts Insulin Resistance But Not Endothelial Function in Young, Healthy Adolescents J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4615 - 4621. [Abstract] [Full Text] [PDF]
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C. S. Mantzoros, T. Li, J. E. Manson, J. B. Meigs, and F. B. Hu Circulating Adiponectin Levels Are Associated with Better Glycemic Control, More Favorable Lipid Profile, and Reduced Inflammation in Women with Type 2 Diabetes J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4542 - 4548. [Abstract] [Full Text] [PDF]
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J. Park, H. K. Rho, K. H. Kim, S. S. Choe, Y. S. Lee, and J. B. Kim Overexpression of Glucose-6-Phosphate Dehydrogenase Is Associated with Lipid Dysregulation and Insulin Resistance in Obesity Mol. Cell. Biol., June 15, 2005; 25(12): 5146 - 5157. [Abstract] [Full Text] [PDF]
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 K Yamamoto, T Kiyohara, Y Murayama, S Kihara, Y Okamoto, T Funahashi, T Ito, R Nezu, S Tsutsui, J-I Miyagawa, et al. Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease Gut, June 1, 2005; 54(6): 789 - 796. [Abstract] [Full Text] [PDF]
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A. H. Berg and P. E. Scherer Adipose Tissue, Inflammation, and Cardiovascular Disease Circ. Res., May 13, 2005; 96(9): 939 - 949. [Abstract] [Full Text] [PDF]
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A. Xu, K. W. Chan, R. L. C. Hoo, Y. Wang, K. C. B. Tan, J. Zhang, B. Chen, M. C. Lam, C. Tse, G. J. S. Cooper, et al. Testosterone Selectively Reduces the High Molecular Weight Form of Adiponectin by Inhibiting Its Secretion from Adipocytes J. Biol. Chem., May 6, 2005; 280(18): 18073 - 18080. [Abstract] [Full Text] [PDF]
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Y. Wang, K. S. L. Lam, J. Y. Xu, G. Lu, L. Y. Xu, G. J. S. Cooper, and A. Xu Adiponectin Inhibits Cell Proliferation by Interacting with Several Growth Factors in an Oligomerization-dependent Manner J. Biol. Chem., May 6, 2005; 280(18): 18341 - 18347. [Abstract] [Full Text] [PDF]
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T. Kadowaki and T. Yamauchi Adiponectin and Adiponectin Receptors Endocr. Rev., May 1, 2005; 26(3): 439 - 451. [Abstract] [Full Text] [PDF]
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H. Satoh, M.T. A. Nguyen, M. Trujillo, T. Imamura, I. Usui, P. E. Scherer, and J. M. Olefsky Adenovirus-Mediated Adiponectin Expression Augments Skeletal Muscle Insulin Sensitivity in Male Wistar Rats Diabetes, May 1, 2005; 54(5): 1304 - 1313. [Abstract] [Full Text] [PDF]
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D. C. W. Lau, B. Dhillon, H. Yan, P. E. Szmitko, and S. Verma Adipokines: molecular links between obesity and atheroslcerosis Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2031 - H2041. [Abstract] [Full Text] [PDF]
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J. Housova, K. Anderlova, J. Krizova, D. Haluzikova, J. Kremen, T. Kumstyrova, H. Papezova, and M. Haluzik Serum Adiponectin and Resistin Concentrations in Patients with Restrictive and Binge/Purge Form of Anorexia Nervosa and Bulimia Nervosa J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1366 - 1370. [Abstract] [Full Text] [PDF]
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M. I. Yilmaz, A. Sonmez, S. Kilic, T. Celik, N. Bingol, M. Pinar, T. Mumcuoglu, and M. Ozata The association of plasma adiponectin levels with hypertensive retinopathy Eur. J. Endocrinol., February 1, 2005; 152(2): 233 - 240. [Abstract] [Full Text] [PDF]
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H. Waki, T. Yamauchi, J. Kamon, S. Kita, Y. Ito, Y. Hada, S. Uchida, A. Tsuchida, S. Takekawa, and T. Kadowaki Generation of Globular Fragment of Adiponectin by Leukocyte Elastase Secreted by Monocytic Cell Line THP-1 Endocrinology, February 1, 2005; 146(2): 790 - 796. [Abstract] [Full Text] [PDF]
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 M. Ishikawa, J. Kitayama, S. Kazama, T. Hiramatsu, K. Hatano, and H. Nagawa Plasma Adiponectin and Gastric Cancer Clin. Cancer Res., January 15, 2005; 11(2): 466 - 472. [Abstract] [Full Text] [PDF]
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 G. K. Shetty, P. A. Economides, E. S. Horton, C. S. Mantzoros, and A. Veves Circulating Adiponectin and Resistin Levels in Relation to Metabolic Factors, Inflammatory Markers, and Vascular Reactivity in Diabetic Patients and Subjects at Risk for Diabetes Diabetes Care, October 1, 2004; 27(10): 2450 - 2457. [Abstract] [Full Text] [PDF]
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M. Furuhashi, N. Ura, N. Moniwa, Y. Shinshi, H. Kouzu, M. Nishihara, N. Kokubu, T. Takahashi, K.-i. Sakamoto, M. Hayashi, et al. Possible Impairment of Transcardiac Utilization of Adiponectin in Patients With Type 2 Diabetes Diabetes Care, September 1, 2004; 27(9): 2217 - 2221. [Abstract] [Full Text] [PDF]
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D. Nagata, R. Takeda, M. Sata, H. Satonaka, E. Suzuki, T. Nagano, and Y. Hirata AMP-Activated Protein Kinase Inhibits Angiotensin II-Stimulated Vascular Smooth Muscle Cell Proliferation Circulation, July 27, 2004; 110(4): 444 - 451. [Abstract] [Full Text] [PDF]
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 G. W. Wong, J. Wang, C. Hug, T.-S. Tsao, and H. F. Lodish A family of Acrp30/adiponectin structural and functional paralogs PNAS, July 13, 2004; 101(28): 10302 - 10307. [Abstract] [Full Text] [PDF]
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R. Shibata, N. Ouchi, S. Kihara, K. Sato, T. Funahashi, and K. Walsh Adiponectin Stimulates Angiogenesis in Response to Tissue Ischemia through Stimulation of AMP-activated Protein Kinase Signaling J. Biol. Chem., July 2, 2004; 279(27): 28670 - 28674. [Abstract] [Full Text] [PDF]
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A. M. Sharma Is There a Rationale for Angiotensin Blockade in the Management of Obesity Hypertension? Hypertension, July 1, 2004; 44(1): 12 - 19. [Abstract] [Full Text] [PDF]
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 S. Klein, L. Fontana, V. L. Young, A. R. Coggan, C. Kilo, B. W. Patterson, and B. S. Mohammed Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease N. Engl. J. Med., June 17, 2004; 350(25): 2549 - 2557. [Abstract] [Full Text] [PDF]
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S. E. Epstein, E. Stabile, T. Kinnaird, C. W. Lee, L. Clavijo, and M. S. Burnett Janus Phenomenon: The Interrelated Tradeoffs Inherent in Therapies Designed to Enhance Collateral Formation and Those Designed to Inhibit Atherogenesis Circulation, June 15, 2004; 109(23): 2826 - 2831. [Full Text] [PDF]
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B. J. Goldstein and R. Scalia Adiponectin: A Novel Adipokine Linking Adipocytes and Vascular Function J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2563 - 2568. [Abstract] [Full Text] [PDF]
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A. M. Xydakis, C. C. Case, P. H. Jones, R. C. Hoogeveen, M.-Y. Liu, E. O. Smith, K. W. Nelson, and C. M. Ballantyne Adiponectin, Inflammation, and the Expression of the Metabolic Syndrome in Obese Individuals: The Impact of Rapid Weight Loss through Caloric Restriction J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2697 - 2703. [Abstract] [Full Text] [PDF]
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J. B. Seo, H. M. Moon, M. J. Noh, Y. S. Lee, H. W. Jeong, E. J. Yoo, W. S. Kim, J. Park, B.-S. Youn, J. W. Kim, et al. Adipocyte Determination- and Differentiation-dependent Factor 1/Sterol Regulatory Element-binding Protein 1c Regulates Mouse Adiponectin Expression J. Biol. Chem., May 21, 2004; 279(21): 22108 - 22117. [Abstract] [Full Text] [PDF]
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M. Kumada, S. Kihara, N. Ouchi, H. Kobayashi, Y. Okamoto, K. Ohashi, K. Maeda, H. Nagaretani, K. Kishida, N. Maeda, et al. Adiponectin Specifically Increased Tissue Inhibitor of Metalloproteinase-1 Through Interleukin-10 Expression in Human Macrophages Circulation, May 4, 2004; 109(17): 2046 - 2049. [Abstract] [Full Text] [PDF]
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M. Komatsu, H. Ohfusa, Y. Sato, H. Yajima, K. Yamauchi, T. Aizawa, and K. Hashizume Strong Inverse Correlation Between Serum Adiponectin Level and Heart Rate-Corrected QT Interval in an Apparently Healthy Population: A suggestion for a direct antiatherogenic effect of adiponectin Diabetes Care, May 1, 2004; 27(5): 1237 - 1238. [Full Text] [PDF]
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 T. Pischon, C. J. Girman, G. S. Hotamisligil, N. Rifai, F. B. Hu, and E. B. Rimm Plasma Adiponectin Levels and Risk of Myocardial Infarction in Men JAMA, April 14, 2004; 291(14): 1730 - 1737. [Abstract] [Full Text] [PDF]
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