Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
Published Online
on March 5, 2007

Circulation. 2007
Published online before print March 5, 2007, doi: 10.1161/CIRCULATIONAHA.106.666941
A more recent version of this article appeared on March 20, 2007
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
115/11/1408    most recent
CIRCULATIONAHA.106.666941v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tao, L.
Right arrow Articles by Ma, X. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tao, L.
Right arrow Articles by Ma, X. L.
Related Collections
Right arrow Apoptosis
Right arrow Acute myocardial infarction
Right arrow Oxidant stress

Submitted on September 26, 2006
Accepted on January 5, 2007

Adiponectin Cardioprotection After Myocardial Ischemia/Reperfusion Involves the Reduction of Oxidative/Nitrative Stress

Ling Tao MD, PhD, Erhe Gao MD, PhD, Xiangying Jiao MD, PhD, Yuexing Yuan PhD, Shuzhuang Li MD, Theodore A. Christopher MD, Bernard L. Lopez MD, Walter Koch PhD, Lawrence Chan MBBS, DSc, Barry J. Goldstein MD, PhD, and Xin L. Ma MD, PhD*

From the Department of Emergency Medicine (L.T., X.J., Y.Y., S.L., T.A.C., B.L.P., X.L.M.), Center for Translational Medicine (E.G., W.K.), and Division of Endocrinology, Diabetes, and Metabolic Diseases (B.J.G.), Thomas Jefferson University, Philadelphia, Pa; and Section of Diabetes, Endocrinology, and Metabolism (L.C.), Department of Medicine, Baylor College of Medicine, Houston, Tex.

* To whom correspondence should be addressed. E-mail: xin.ma{at}jefferson.edu.

Background--Several clinical studies have demonstrated that levels of adiponectin are significantly reduced in patients with type 2 diabetes and that adiponectin levels are inversely related to the risk of myocardial ischemia. The present study was designed to determine the mechanism by which adiponectin exerts its protective effects against myocardial ischemia/reperfusion.

Methods and Results--Adiponectin-/- or wild-type mice were subjected to 30 minutes of myocardial ischemia followed by 3 hours or 24 hours (infarct size and cardiac function) of reperfusion. Myocardial infarct size and apoptosis, production of peroxynitrite, nitric oxide (NO) and superoxide, and inducible NO synthase (iNOS) and gp91phox protein expression were compared. Myocardial apoptosis and infarct size were markedly enhanced in adiponectin-/- mice (P<0.01). Formation of NO, superoxide, and their cytotoxic reaction product, peroxynitrite, were all significantly higher in cardiac tissue obtained from adiponectin-/- than from wild-type mice (P<0.01). Moreover, myocardial ischemia/reperfusion-induced iNOS and gp91phox protein expression was further enhanced, but endothelial NOS phosphorylation was reduced in cardiac tissue from adiponectin-/- mice. Administration of the globular domain of adiponectin 10 minutes before reperfusion reduced myocardial ischemia/reperfusion-induced iNOS/gp91phox protein expression, decreased NO/superoxide production, blocked peroxynitrite formation, and reversed proapoptotic and infarct-enlargement effects observed in adiponectin-/- mice.

Conclusion--The present study demonstrates that adiponectin is a natural molecule that protects hearts from ischemia/reperfusion injury by inhibition of iNOS and nicotinamide adenine dinucleotide phosphate-oxidase protein expression and resultant oxidative/nitrative stress.


Key words: apoptosis • diabetes mellitus • myocardial infarction




This article has been cited by other articles:


Home page
Cardiovasc ResHome page
M. Karmazyn, D. M. Purdham, V. Rajapurohitam, and A. Zeidan
Signalling mechanisms underlying the metabolic and other effects of adipokines on the heart
Cardiovasc Res, July 15, 2008; 79(2): 279 - 286.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
K. Fujita, N. Maeda, M. Sonoda, K. Ohashi, T. Hibuse, H. Nishizawa, M. Nishida, A. Hiuge, A. Kurata, S. Kihara, et al.
Adiponectin Protects Against Angiotensin II-Induced Cardiac Fibrosis Through Activation of PPAR-{alpha}
Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 863 - 870.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
A. T. Gonon, U. Widegren, A. Bulhak, F. Salehzadeh, J. Persson, P.-O. Sjoquist, and J. Pernow
Adiponectin protects against myocardial ischaemia-reperfusion injury via AMP-activated protein kinase, Akt, and nitric oxide
Cardiovasc Res, April 1, 2008; 78(1): 116 - 122.
[Abstract] [Full Text] [PDF]


Home page
J ANIM SCIHome page
N. K. Gabler and M. E. Spurlock
Integrating the immune system with the regulation of growth and efficiency
J Anim Sci, April 1, 2008; 86(14_suppl): E64 - E74.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
M. Nishimura, Y. Izumiya, A. Higuchi, R. Shibata, J. Qiu, C. Kudo, H. K. Shin, M. A. Moskowitz, and N. Ouchi
Adiponectin Prevents Cerebral Ischemic Injury Through Endothelial Nitric Oxide Synthase Dependent Mechanisms
Circulation, January 15, 2008; 117(2): 216 - 223.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
K. Shinmura, K. Tamaki, K. Saito, Y. Nakano, T. Tobe, and R. Bolli
Cardioprotective Effects of Short-Term Caloric Restriction Are Mediated by Adiponectin via Activation of AMP-Activated Protein Kinase
Circulation, December 11, 2007; 116(24): 2809 - 2817.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Saito, D. Fujioka, K.-i. Kawabata, T. Kobayashi, T. Yano, T. Nakamura, Y. Kodama, H. Takano, Y. Kitta, J.-e. Obata, et al.
Statin reverses reduction of adiponectin receptor expression in infarcted heart and in TNF-{alpha}-treated cardiomyocytes in association with improved glucose uptake
Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3490 - H3497.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
K. Ohashi, H. Iwatani, S. Kihara, Y. Nakagawa, N. Komura, K. Fujita, N. Maeda, M. Nishida, F. Katsube, I. Shimomura, et al.
Exacerbation of Albuminuria and Renal Fibrosis in Subtotal Renal Ablation Model of Adiponectin-Knockout Mice
Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1910 - 1917.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
B. J. Goldstein, R. Scalia, X. L. Ma, K. Mahadev, X. Wu, and R. Ouedraogo
Comment on: Hattori et al. (2007) Globular Adiponectin Activates Nuclear Factor-{kappa}B and Activating Protein-1 and Enhances Angiotensin II-Induced Proliferation in Cardiac Fibroblasts: Diabetes 56:804-808
Diabetes, July 1, 2007; 56(7): e7 - e8.
[Full Text] [PDF]