Pioglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, Attenuates Myocardial Ischemia/Reperfusion Injury in a Rat Model
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Thiazolidinediones are insulin-sensitizing drugs, ligands for peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which play an important role in the modulation of inflammatory responses. Myocardial ischemia/reperfusion (MI/R) injury is associated with inflammation, in which various cells, particularly monocytes and macrophages, are involved. This study examined the effects of the thiazolidinedione peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, in a rat model of MI/R injury. Pioglitazone at 3 mg/kg/day or the vehicle was administered for 7 days before rats were subjected to 30 minutes of coronary ligation followed by 24 hours of reperfusion. The mRNA expression [monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1] in the ischemic region, the number of infiltrating macrophages in the ischemic region, and the myocardial infarct size were examined. The inhibitory effects of pioglitazone on activated macrophages were studied in vitro. Phorbol 12-myristate 13-acetate-induced MCP-1 production, in the absence or presence of pioglitazone, were assayed in cultured macrophages. Compared with the control group, (1). mRNA levels of MCP-1 and intercellular adhesion molecule-1 and the number of infiltrating macrophages in the ischemic region were significantly lower in the pioglitazone-treated group; and (2). myocardial infarct size was significantly smaller in the pioglitazone-treated group. Phorbol 12-myristate 13-acetate-stimulated cultured macrophages in the presence of pioglitazone produced significantly lower levels of MCP-1 than the stimulated control in the absence of pioglitazone. These observations demonstrate that pioglitazone has anti-inflammatory effects in MI/R injury that are independent of its insulin-sensitizing effect.
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Studies in nondiabetic rats have shown a positive benefit of TZD treatment upon ischemia/reperfusion, although this has not been shown to be true for other models such as pigs.
“Studies in nondiabetic rats have also shown a positive benefit of TZD treatment upon ischemia/reperfusion (158, 176, 390), although this has not been shown to be true for other models such as pigs (380).”
From Cardiac remodeling in obesity (2008) · cites this paper as [158]
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Cites
Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M., & Kliewer, S. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.22.12953 · Cited by 3,626 · see citing works
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor
Tontonoz, P., Hu, E., & Spiegelman, B. M. (1994) · Cell · doi:10.1016/0092-8674(94)90006-x · Cited by 3,533 · see citing works
The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J., & Glass, C. K. (1998) · Nature · doi:10.1038/34178 · Cited by 3,525 · see citing works
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
Jiang, C., Ting, A. T., & Seed, B. (1998) · Nature · doi:10.1038/34184 · Cited by 2,899 · see citing works
Myocardial reperfusion: a double-edged sword?
D, E. B. M., & Kloner, R. A. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112160 · Cited by 1,368 · see citing works
Lehmann, J. M., Lenhard, J. M., Oliver, B. B., Ringold, G. M., & Kliewer, S. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3406 · Cited by 1,110 · see citing works
Chawla, A., Schwarz, E. J., Dimaculangan, D. D., & Lazar, M. A. (1994) · Endocrinology · doi:10.1210/endo.135.2.8033830 · Cited by 874 · see citing works
A novel therapy for colitis utilizing PPAR-γ ligands to inhibit the epithelial inflammatory response
Su, C. G., Wen, X., Bailey, S. T., Jiang, W. G., Rangwala, S. M., Keilbaugh, S. A., Flanigan, A., Murthy, S., Lazar, M. A., & Wu, G. D. (1999) · Journal of Clinical Investigation · doi:10.1172/jci7145 · Cited by 769 · see citing works
Shyng, S., Lehmann, S., Moulder, K. L., & Harris, D. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.50.30221 · Cited by 704 · see citing works
Lemberger, T., Desvergne, B., & Wahli, W. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.335 · Cited by 704 · see citing works
Ono, K., Matsumori, A., Shioi, T., Furukawa, Y., & Sasayama, S. (1998) · Circulation · doi:10.1161/01.cir.98.2.149 · Cited by 459 · see citing works
Self-citationDesreumaux, P., Dubuquoy, L., Nutten, S., Peuchmaur, M. M., Englaro, W., Schoonjans, K., Dérijard, B., Desvergne, B., Wahli, W., Chambon, P., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.7.827 · Cited by 458 · see citing works
Cytokine mRNA expression in postischemic/reperfused myocardium.
Herskowitz, A., Choi, S. J., Ansari, A. A., & Wesselingh, S. L. (1995) · Europe PMC (PubMed Central) · Cited by 374 · see citing works
Wayman, N. S., Hattori, Y., McDonald, M. C., Mota‐Filipe, H., Cuzzocrea, S., PISANO, B., Chatterjee, P. K., & Thiemermann, C. (2002) · The FASEB Journal · doi:10.1096/fj.01-0793com · Cited by 361 · see citing works
Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone.
Sakamoto, J., Kimura, H., Moriyama, S., Odaka, H., Momose, Y., Sugiyama, Y., & Sawada, H. (2000) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.2000.3868 · Cited by 313 · see citing works
Yue, T.-L., Chen, J., Bao, W., Narayanan, P. K., Bril, A., Jiang, W., Lysko, P. G., Gu, J.-L., Boyce, R., Zimmerman, D. M., et al. (2001) · Circulation · doi:10.1161/hc4601.099403 · Cited by 295 · see citing works
The Human Homolog of the JE Gene Encodes a Monocyte Secretory Protein
Rollins, B. J., Stier, P., Ernst, T. J., & Wong, G. G. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.11.4687-4695.1989 · Cited by 239 · see citing works
Zachariae, C. O. C., Anderson, A. O., Thompson, H. L., Appella, E., Mantovani, A., Oppenheim, J. J., & Matsushima, K. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.6.2177 · Cited by 238 · see citing works
Schoonjans, K., & Auwerx, J. H. (2000) · The Lancet · doi:10.1016/s0140-6736(00)90002-3 · Cited by 233 · see citing works
Kukielka, G. L., Hawkins, H. K., Michael, L., Manning, A., Youker, K. A., Lane, C. L., Entman, M. L., Smith, C. W., & Anderson, D. C. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116729 · Cited by 230 · see citing works
Camp, H. S., Li, O., Wise, S., Hong, Y., Frankowski, C., Shen, X., Vanbogelen, R., & Leff, T. (2000) · Diabetes · doi:10.2337/diabetes.49.4.539 · Cited by 224 · see citing works
Shioi, T., Matsumori, A., Kihara, Y., Inoko, M., Ono, K., Iwanaga, Y., Yamada, T., Iwasaki, A., Matsushima, K., & Sasayama, S. (1997) · Circulation Research · doi:10.1161/01.res.81.5.664 · Cited by 162 · see citing works
Self-citationMatsumori, A., Furukawa, Y., Hashimoto, T., Yoshida, A., Ono, K., Shioi, T., Okada, M., Iwasaki, A., Nishio, R., Matsushima, K., et al. (1997) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1996.0285 · Cited by 152 · see citing works
Self-citation(1997) · PubMed · Cited by 139 · see citing works
Robinson, E. A., Yoshimura, T., Leonard, E. J., Tanaka, S., Griffin, P. R., Shabanowitz, J., Hunt, D. F., & Appella, E. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.6.1850 · Cited by 135 · see citing works
Uchimura, K., Nakamuta, M., Enjoji, M., Irie, T., Sugimoto, R., Muta, T., Iwamoto, H., & Nawata, H. (2001) · Hepatology · doi:10.1053/jhep.2001.21145 · Cited by 126 · see citing works
Behr, T. M., Wang, X., Aiyar, N. V., Coatney, R. W., Li, X., Koster, P. D., Angermann, C. E., Ohlstein, E. H., Feuerstein, G., & Winaver, J. M. (2000) · Circulation · doi:10.1161/01.cir.102.11.1315 · Cited by 115 · see citing works
Kakio, T., Matsumori, A., Ono, K., et al. (2000) · Laboratory Investigation · doi:10.1038/labinvest.3780119 · Cited by 95 · see citing works
Self-citationOno, K., Matsumori, A., Furukawa, Y., Igata, H., Shioi, T., Matsushima, K., & Sasayama, S. (1999) · PubMed · Cited by 92 · see citing works
Self-citationGumina, R. J., Schultz, J. E. J., Yao, Z., et al. (1996) · Circulation · doi:10.1161/01.cir.94.12.3327 · Cited by 91 · see citing works
Ikeda, U., Ikeda, M., Seino, Y., et al. (1993) · Atherosclerosis · doi:10.1016/0021-9150(93)90176-u · Cited by 58 · see citing works
Hartman, J. C., Anderson, D. C., Wiltse, A. L., et al. (1995) · Cardiovascular Research · doi:10.1016/s0008-6363(95)00015-1 · Cited by 54 · see citing works
Production of monocyte chemoattractant protein-1 by bovine glomerular endothelial cells
KAKIZAKI, Y., Waga, S., Sugimoto, K., et al. (1995) · Kidney International · doi:10.1038/ki.1995.485 · Cited by 50 · see citing works
Ban, K., Ikeda, U., Takahashi, M., et al. (1994) · Cardiovascular Research · doi:10.1093/cvr/28.8.1258 · Cited by 47 · see citing works
Ioculano, M., Squadrito, F., Altavilla, D., et al. (1994) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)00452-8 · Cited by 41 · see citing works
Haslinger, B., Mandl–Weber, S., Sellmayer, A., et al. (2001) · The Nephron journals/Nephron journals · doi:10.1159/000045941 · Cited by 24 · see citing works
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Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736 · see citing works
Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists
Kapadia, R. (2008) · Frontiers in Bioscience · doi:10.2741/2802 · Cited by 433 · see citing works
Yue, T.-L., Bao, W., Gu, J.-L., Cui, J., Tao, L., Ma, X.-L., Ohlstein, E. H., & Jucker, B. M. (2005) · Diabetes · doi:10.2337/diabetes.54.2.554 · Cited by 170 · see citing works
PPAR-γ activation fails to provide myocardial protection in ischemia and reperfusion in pigs
Xu, Y., Gen, M., Lu, L., Fox, J., Weiss, S. O., Brown, R. D., Perlov, D., Ahmad, H., Zhu, P., Greyson, C., et al. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00618.2004 · Cited by 49 · see citing works
- Authors
- Ito, H., Nakano, A., Kinoshita, M., & Matsumori, A.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Matsumori, Akira
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 83
- Issue
- 12
- Pages
- 1715-1721
- ISSN
- 0023-6837 (ISSN-L)
- OpenAlex
- W2019235722
- Cited by
- 104
- References
- 36
- Citations by year
- 2025: 3 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 4 · 2013: 6 · 2012: 2
- FWCI
- 6.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- pioglitazone, PPARγ agonists, thiazolidinediones, myocardial ischemia-reperfusion injury, myocardial infarct size, macrophage infiltration, MCP-1, ICAM-1, inflammation, anti-inflammatory activity, coronary artery ligation
- MeSH terms
- Pioglitazone, Animals, Disease Models, Animal, Hypoglycemic Agents, Macrophage Activation, Macrophages, Male, Myocardial Infarction, RNA, Messenger, Tetradecanoylphorbol Acetate, Transcription Factors, Myocardial Reperfusion Injury, Rats, Wistar, Receptors, Cytoplasmic and Nuclear, Intercellular Adhesion Molecule-1, Chemokine CCL2, Thiazolidinediones, Rats
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