Circulation. 2001;104:2588-2594
doi: 10.1161/hc4601.099403
doi: 10.1161/hc4601.099403
(Circulation. 2001;104:2588.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
In Vivo Myocardial Protection From Ischemia/Reperfusion Injury by the Peroxisome Proliferator–Activated Receptor-
Agonist Rosiglitazone
From the Departments of Cardiovascular Pharmacology (T.Y., J.C., W.B., A.B., W.J., P.G.L., J.G., R.E.B., E.H.O.) and Safety Assessment (P.K.N., R.B., D.M.Z., T.K.H.), GlaxoSmithKline Pharmaceuticals, King of Prussia, Pa.
Correspondence to Tian-li Yue, PhD, Department of Cardiovascular Pharmacology, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Rd, PO Box 1539, UW2510, King of Prussia, PA 19406. E-mail tian-li_yue{at}sbphrd.com
Background Diabetes is associated with increased risk of mortality as a consequence of acute myocardial infarction. This study determined whether rosiglitazone (ROSI) could reduce myocardial infarction after ischemia/reperfusion injury.
Methods and Results Male Lewis rats were anesthetized, and the left anterior descending coronary artery was ligated for 30 minutes. After reperfusion for 24 hours, the ischemic and infarct sizes were determined. ROSI at 1 and 3 mg/kg IV reduced infarct size by 30% and 37%, respectively (P<0.01 versus vehicle). Pretreatment with ROSI (3 mg · kg-1 · d-1 PO) for 7 days also reduced infarct size by 24% (P<0.01). ROSI also improved ischemia/reperfusion-induced myocardial contractile dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in ROSI-treated rats. ROSI reduced the accumulation of neutrophils and macrophages in the ischemic heart by 40% and 43%, respectively (P<0.01). Ischemia/reperfusion induced upregulation of CD11b/CD18 and downregulation of L-selectin on neutrophils and monocytes; these effects were significantly attenuated in ROSI-treated animals. Likewise, intercellular adhesion molecule-1 expression in ischemic hearts was markedly diminished by ROSI, as was the ischemia/reperfusion-stimulated upregulation of monocyte chemoattractant protein-1.
Conclusions ROSI reduced myocardial infarction and improved contractile dysfunction caused by ischemia/reperfusion injury. The cardioprotective effect of ROSI was most likely due to inhibition of the inflammatory response.
Key Words: ischemia • myocardial infarction • diabetes • PPAR-
• rosiglitazone
This article has been cited by other articles:
 |
|
 |
|
  Y. Tanaka, T. Hasegawa, Z. Chen, Y. Okita, and K. Okada Renoprotective immunosuppression by pioglitazone with low-dose cyclosporine in rat heart transplantation J. Thorac. Cardiovasc. Surg., September 1, 2009; 138(3): 744 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jones, R. Deb, E. Torsney, F. Howe, M. Dunkley, Y. Gnaneswaran, D. Gaze, H. Nasr, I. M. Loftus, M. M. Thompson, et al. Rosiglitazone Reduces the Development and Rupture of Experimental Aortic Aneurysms Circulation, June 23, 2009; 119(24): 3125 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Wu, W.-M. Cheung, Y.-S. Tsai, Y.-T. Chen, W.-H. Fong, H.-D. Tsai, Y.-C. Chen, J.-Y. Liou, S.-K. Shyue, J.-J. Chen, et al. Ligand-Activated Peroxisome Proliferator-Activated Receptor-{gamma} Protects Against Ischemic Cerebral Infarction and Neuronal Apoptosis by 14-3-3{epsilon} Upregulation Circulation, March 3, 2009; 119(8): 1124 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Han, Y. Horie, J.-Y. Fan, K. Sun, J. Guo, S. Miura, and T. Hibi Potential of 3,4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery Am J Physiol Gastrointest Liver Physiol, January 1, 2009; 296(1): G36 - G44. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ye, Y. Lin, S. Manickavasagam, J. R. Perez-Polo, B. C. Tieu, and Y. Birnbaum Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2436 - H2446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Collino, N. S.A. Patel, and C. Thiemermann Review: PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury Therapeutic Advances in Cardiovascular Disease, June 1, 2008; 2(3): 179 - 197. [Abstract] [PDF]
|
|
|
|
 |
|
 T.-L. Yue, S. S. Nerurkar, W. Bao, B. M. Jucker, L. Sarov-Blat, K. Steplewski, E. H. Ohlstein, and R. N. Willette In Vivo Activation of Peroxisome Proliferator-Activated Receptor-{delta} Protects the Heart from Ischemia/Reperfusion Injury in Zucker Fatty Rats J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 466 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Napimoga, S. M. Vieira, D. Dal-Secco, A. Freitas, F. O. Souto, F. L. Mestriner, J. C. Alves-Filho, R. Grespan, T. Kawai, S. H. Ferreira, et al. Peroxisome Proliferator-Activated Receptor-{gamma} Ligand, 15-Deoxy-{Delta}12,14-Prostaglandin J2, Reduces Neutrophil Migration via a Nitric Oxide Pathway J. Immunol., January 1, 2008; 180(1): 609 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. N. Finck The PPAR regulatory system in cardiac physiology and disease Cardiovasc Res, January 15, 2007; 73(2): 269 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nagai, Y. Oike, K. Izumi-Nagai, T. Urano, Y. Kubota, K. Noda, Y. Ozawa, M. Inoue, K. Tsubota, T. Suda, et al. Angiotensin II Type 1 Receptor-Mediated Inflammation Is Required for Choroidal Neovascularization Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2252 - 2259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B Patle, J. A De Lemos, K. L Wyne, and D. K McGuire Thiazolidinediones and risk for atherosclerosis: pleiotropic effects of PPAR{gamma} agonism Diabetes and Vascular Disease Research, September 1, 2006; 3(2): 65 - 71. [Abstract] [PDF]
|
|
|
|
|
|
Y. Ye, Y. Lin, S. Atar, M.-H. Huang, J. R. Perez-Polo, B. F. Uretsky, and Y. Birnbaum Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1158 - H1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Molavi, J. Chen, and J. L. Mehta Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H687 - H693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, L. Lu, C. Greyson, M. Rizeq, K. Nunley, B. Wyatt, M. R. Bristow, C. S. Long, and G. G. Schwartz The PPAR-{alpha} activator fenofibrate fails to provide myocardial protection in ischemia and reperfusion in pigs Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1798 - H1807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-N. Lin, W.-M. Cheung, J.-S. Wu, J.-J. Chen, H. Lin, J.-J. Chen, J.-Y. Liou, S.-K. Shyue, and K. K. Wu 15d-Prostaglandin J2 Protects Brain From Ischemia-Reperfusion Injury Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 481 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Johns, Z. Ao, M. Eybye, A. Olzinski, M. Costell, S. Gruver, S. A. Smith, S. A. Douglas, and C. H. Macphee Rosiglitazone Protects against Ischemia/Reperfusion-Induced Leukocyte Adhesion in the Zucker Diabetic Fatty Rat J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1020 - 1027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lautamaki, K.E. J. Airaksinen, M. Seppanen, J. Toikka, M. Luotolahti, E. Ball, R. Borra, R. Harkonen, P. Iozzo, M. Stewart, et al. Rosiglitazone Improves Myocardial Glucose Uptake in Patients With Type 2 Diabetes and Coronary Artery Disease: A 16-Week Randomized, Double-Blind, Placebo-Controlled Study Diabetes, September 1, 2005; 54(9): 2787 - 2794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Patel, K. L Wyne, and D. K McGuire Thiazolidinediones, peripheral oedema and congestive heart failure: what is the evidence? Diabetes and Vascular Disease Research, May 1, 2005; 2(2): 61 - 66. [Abstract] [PDF]
|
|
|
|
|
|
A. Sivarajah, M. C. McDonald, and C. Thiemermann The Cardioprotective Effects of Preconditioning with Endotoxin, but Not Ischemia, Are Abolished by a Peroxisome Proliferator-Activated Receptor-{gamma} Antagonist J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 896 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Ertl and S. Frantz Healing after myocardial infarction Cardiovasc Res, April 1, 2005; 66(1): 22 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abdelrahman, A. Sivarajah, and C. Thiemermann Beneficial effects of PPAR-{gamma} ligands in ischemia-reperfusion injury, inflammation and shock Cardiovasc Res, March 1, 2005; 65(4): 772 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, K. Chen, N. Sinha, X. Zhang, Y. Wang, A. K. Sinha, F. Romeo, and J. L. Mehta The effects of PPAR-{gamma} ligand pioglitazone on platelet aggregation and arterial thrombus formation Cardiovasc Res, March 1, 2005; 65(4): 907 - 912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin Peroxisome proliferator-activated receptors and cardiovascular remodeling Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1037 - H1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, M. Gen, L. Lu, J. Fox, S. O. Weiss, R. D. Brown, D. Perlov, H. Ahmad, P. Zhu, C. Greyson, et al. PPAR-{gamma} activation fails to provide myocardial protection in ischemia and reperfusion in pigs Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1314 - H1323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-L. Yue, W. Bao, J.-L. Gu, J. Cui, L. Tao, X.-L. Ma, E. H. Ohlstein, and B. M. Jucker Rosiglitazone Treatment in Zucker Diabetic Fatty Rats Is Associated With Ameliorated Cardiac Insulin Resistance and Protection From Ischemia/Reperfusion-Induced Myocardial Injury Diabetes, February 1, 2005; 54(2): 554 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Villarreal and J. Asbun Peroxisome Proliferator-Activated Receptors Ligands, Oxidative Stress, and Cardiac Fibroblast Extracellular Matrix Turnover Hypertension, November 1, 2004; 44(5): 621 - 622. [Full Text] [PDF]
|
|
|
|
|
|
K. Chen, J. Chen, D. Li, X. Zhang, and J. L. Mehta Angiotensin II Regulation of Collagen Type I Expression in Cardiac Fibroblasts: Modulation by PPAR-{gamma} Ligand Pioglitazone Hypertension, November 1, 2004; 44(5): 655 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Akaike, W. Che, N.-L. Marmarosh, S. Ohta, M. Osawa, B. Ding, B. C. Berk, C. Yan, and J.-i. Abe The Hinge-Helix 1 Region of Peroxisome Proliferator-Activated Receptor {gamma}1 (PPAR{gamma}1) Mediates Interaction with Extracellular Signal-Regulated Kinase 5 and PPAR{gamma}1 Transcriptional Activation: Involvement in Flow-Induced PPAR{gamma} Activation in Endothelial Cells Mol. Cell. Biol., October 1, 2004; 24(19): 8691 - 8704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nian, P. Lee, N. Khaper, and P. Liu Inflammatory Cytokines and Postmyocardial Infarction Remodeling Circ. Res., June 25, 2004; 94(12): 1543 - 1553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Marx, H. Duez, J.-C. Fruchart, and B. Staels Peroxisome Proliferator-Activated Receptors and Atherogenesis: Regulators of Gene Expression in Vascular Cells Circ. Res., May 14, 2004; 94(9): 1168 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-R. Liu, L. Tao, E. Gao, B. L Lopez, T. A Christopher, R. N Willette, E. H Ohlstein, T.-L. Yue, and X.-L. Ma Anti-apoptotic effects of rosiglitazone in hypercholesterolemic rabbits subjected to myocardial ischemia and reperfusion Cardiovasc Res, April 1, 2004; 62(1): 135 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Bao, E. Hu, L. Tao, R. Boyce, R. Mirabile, D. T Thudium, X.-l. Ma, R. N Willette, and T.-l. Yue Inhibition of Rho-kinase protects the heart against ischemia/reperfusion injury Cardiovasc Res, February 15, 2004; 61(3): 548 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Chatterjee, N. S.A Patel, S. Cuzzocrea, P. A.J Brown, K. N Stewart, H. Mota-Filipe, D. Britti, W. Eberhardt, J. Pfeilschifter, and C. Thiemermann The cyclopentenone prostaglandin 15-deoxy-{Delta}12,14-prostaglandin J2 ameliorates ischemic acute renal failure Cardiovasc Res, February 15, 2004; 61(3): 630 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Nesto, D. Bell, R. O. Bonow, V. Fonseca, S. M. Grundy, E. S. Horton, M. Le Winter, D. Porte, C. F. Semenkovich, S. Smith, et al. Thiazolidinedione Use, Fluid Retention, and Congestive Heart Failure: A consensus statement from the American Heart Association and American Diabetes Association Diabetes Care, January 1, 2004; 27(1): 256 - 263. [Full Text] [PDF]
|
|
|
|
|
|
R. W. Nesto, D. Bell, R. O. Bonow, V. Fonseca, S. M. Grundy, E. S. Horton, M. Le Winter, D. Porte, C. F. Semenkovich, S. Smith, et al. Thiazolidinedione Use, Fluid Retention, and Congestive Heart Failure: A Consensus Statement From the American Heart Association and American Diabetes Association Circulation, December 9, 2003; 108(23): 2941 - 2948. [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Mehrabi, P. Haslmayer, S. Humpeler, G. Strauss-Blasche, W. Marktl, F. Tamaddon, N. Serbecic, G. Wieselthaler, T. Thalhammer, H. D. Glogar, et al. Quantitative analysis of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) expression in arteries and hearts of patients with ischaemic or dilated cardiomyopathy Eur J Heart Fail, December 1, 2003; 5(6): 733 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Mehta, B. Hu, J. Chen, and D. Li Pioglitazone Inhibits LOX-1 Expression in Human Coronary Artery Endothelial Cells by Reducing Intracellular Superoxide Radical Generation Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2203 - 2208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-l. Yue, W. Bao, B. M. Jucker, J.-l. Gu, A. M. Romanic, P. J. Brown, J. Cui, D. T. Thudium, R. Boyce, C. L. Burns-Kurtis, et al. Activation of Peroxisome Proliferator-Activated Receptor-{alpha} Protects the Heart From Ischemia/Reperfusion Injury Circulation, November 11, 2003; 108(19): 2393 - 2399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-M. Lee and T.-F. Chou Troglitazone administration limits infarct size by reduced phosphorylation of canine myocardial connexin43 proteins Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1650 - H1659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin, F. Amiri, K. Benkirane, M. Iglarz, and Q. N. Diep Peroxisome Proliferator-Activated Receptors: Vascular and Cardiac Effects in Hypertension Hypertension, October 1, 2003; 42(4): 664 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A Lygate, K. Hulbert, M. Monfared, M. A Cole, K. Clarke, and S. Neubauer The PPAR{gamma}-activator rosiglitazone does not alter remodeling but increases mortality in rats post-myocardial infarction Cardiovasc Res, June 1, 2003; 58(3): 632 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, L. Lu, C. Greyson, J. Lee, M. Gen, K. Kinugawa, C. S. Long, and G. G. Schwartz Deleterious Effects of Acute Treatment With a Peroxisome Proliferator-Activated Receptor-{gamma} Activator in Myocardial Ischemia and Reperfusion in Pigs Diabetes, May 1, 2003; 52(5): 1187 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H. W. Tang, G. S. Francis, B. J. Hoogwerf, and J. B. Young Fluid retention after initiation of thiazolidinedione therapy in diabetic patients with established chronic heart failure J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1394 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Kelly PPARs of the Heart: Three Is a Crowd Circ. Res., March 21, 2003; 92(5): 482 - 484. [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Wang, R. D. Weisel, P. P. Liu, P. W.M. Fedak, and S. Verma Glitazones and Heart Failure: Critical Appraisal for the Clinician Circulation, March 18, 2003; 107(10): 1350 - 1354. [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Tack Insulin Resistance and Acute Cardiovascular Complications Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2003; 7(1): 85 - 90. [PDF]
|
|
|
|
|
|
P. Dandona, A. Aljada, and A. Bandyopadhyay The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia Diabetes Care, February 1, 2003; 26(2): 516 - 519. [Full Text] [PDF]
|
|
|
|
|
|
E. Aasum, A. D. Hafstad, D. L. Severson, and T. S. Larsen Age-Dependent Changes in Metabolism, Contractile Function, and Ischemic Sensitivity in Hearts From db/db Mice Diabetes, February 1, 2003; 52(2): 434 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shiomi, H. Tsutsui, S. Hayashidani, N. Suematsu, M. Ikeuchi, J. Wen, M. Ishibashi, T. Kubota, K. Egashira, and A. Takeshita Pioglitazone, a Peroxisome Proliferator-Activated Receptor-{gamma} Agonist, Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction Circulation, December 10, 2002; 106(24): 3126 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Clay, A. Monjazeb, J. Thorburn, F. H. Chilton, and K. P. High 15-Deoxy-{Delta}12,14-prostaglandin J2-induced apoptosis does not require PPAR{gamma} in breast cancer cells J. Lipid Res., November 1, 2002; 43(11): 1818 - 1828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Haffner, A. S. Greenberg, W. M. Weston, H. Chen, K. Williams, and M. I. Freed Effect of Rosiglitazone Treatment on Nontraditional Markers of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus Circulation, August 6, 2002; 106(6): 679 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. WAYMAN, Y. HATTORI, M. C. MCDONALD, H. MOTA-FILIPE, S. CUZZOCREA, B. PISANO, P. K. CHATTERJEE, and C. THIEMERMANN Ligands of the peroxisome proliferator-activated receptors (PPAR-{gamma} and PPAR-{alpha}) reduce myocardial infarct size FASEB J, July 1, 2002; 16(9): 1027 - 1040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Khandoudi, P. Delerive, I. Berrebi-Bertrand, R. E. Buckingham, B. Staels, and A. Bril Rosiglitazone, a Peroxisome Proliferator-Activated Receptor-{gamma}, Inhibits the Jun NH2-Terminal Kinase/Activating Protein 1 Pathway and Protects the Heart From Ischemia/Reperfusion Injury Diabetes, May 1, 2002; 51(5): 1507 - 1514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Sidell, M. A. Cole, N. J. Draper, M. Desrois, R. E. Buckingham, and K. Clarke Thiazolidinedione Treatment Normalizes Insulin Resistance and Ischemic Injury in the Zucker Fatty Rat Heart Diabetes, April 1, 2002; 51(4): 1110 - 1117. [Abstract] [Full Text] [PDF]
|
|