Cardiovascular Research

Cardiovascular Research 2005 65(2):345-355; doi:10.1016/j.cardiores.2004.10.018

This Article Full Text FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by Birnbaum, Y. Articles by Uretsky, B. F. Search for Related Content PubMed PubMed Citation Articles by Birnbaum, Y. Articles by Uretsky, B. F. Social Bookmarking          What's this?

Copyright © 2004, European Society of Cardiology

Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia–reperfusion injury

Yochai Birnbaum^*, Yumei Ye, Salvatore Rosanio, Shahin Tavackoli, Zhao-Yong Hu, Ernst R. Schwarz and Barry F. Uretsky

The Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, 5,106 John Sealy Annex, 301 University Blvd., Galveston, Texas 77555-0553, United States

^* Corresponding author. Tel.: +1 409 772 2794; fax: +1 409 772 4982. Email address: yobirnba{at}utmb.edu

Objectives: Statins attenuate myocardial ischemic injury by activating nitric oxide synthase (NOS). It is unknown whether cyclooxygenase-2 (COX2), which mediates late ischemic preconditioning, also mediates statins-induced cardioprotection. We investigated the involvement of the prostaglandins and NOS in the cardioprotective effect of atorvastatin (ATV) in the rat.

Methods: Sprague–Dawley rats were randomized to a 3-day oral treatment with ATV 10 mg/kg, valdecoxib, a selective COX2 inhibitor (VAL) 3 mg/kg, ATV+VAL or water alone. Rats underwent 30-min myocardial ischemia followed by 4-h reperfusion.

Results: Infarct size was smaller in the ATV group (31.3 ± 1.9%) than controls (44.5 ± 3.1%; p=0.011) and VAL (44.5 ± 3.1%; p=0.008). VAL attenuated the protective effect of ATV when administered together (40.2 ± 2.5%). ATV pretreatment increased myocardial content of 6-keto-PGF₁ (69.5 ± 1.5 pg/mg) and PGE₂ (57.9 ± 0.6 pg/mg) compared with controls (16.2 ± 0.2 and 42.1 ± 2.0 pg/mg, respectively) and ATV+VAL (15.8 ± 0.3 and 39.9 ± 1.9 pg/mg, respectively). ATV increased myocardial content of cytosolic phospholipase A₂ (cPLA₂) (174.8 ± 0.5%), COX2 (446.2 ± 0.9%), PGI₂ synthase (201.8 ± 1.1%) and PGE₂ synthase (122 ± 0.7%), whereas ATV+VAL did not (123.0 ± 7.9%, 93.8 ± 8.5%, 103.0 ± 1.6% and 99.0 ± 0%, respectively). ATV did not change the myocardial content of eNOS and nNOS, but increased the concentration of phosphorylated eNOS (231.8 ± 2.4%) and iNOS (154.5 ± 1.2%). This effect was not blocked by coadministration of VAL (231.5 ± 3.0% and 154.5 ± 1.8%, respectively).

Conclusions: Our results suggest that the prostaglandins are essential for mediating the myocardial protective effects of ATV and their production is downstream to eNOS phosphorylation and iNOS.

KEYWORDS Cyclooxygenase; Infarction; Phospholipases; Prostaglandins; Statins

---

Time for primary review 23 days

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				Y. Alvarez, C. Municio, S. Alonso, J. A. S. Roman, M. S. Crespo, and N. Fernandez Cyclooxygenase-2 Induced by Zymosan in Human Monocyte-Derived Dendritic Cells Shows High Stability, and Its Expression Is Enhanced by Atorvastatin J. Pharmacol. Exp. Ther., June 1, 2009; 329(3): 987 - 994. [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]

				Y. Ye, Y. Lin, J. R. Perez-Polo, B. F. Uretsky, Z. Ye, B. C. Tieu, and Y. Birnbaum Phosphorylation of 5-Lipoxygenase at Ser523 by Protein Kinase A Determines Whether Pioglitazone and Atorvastatin Induce Proinflammatory Leukotriene B4 or Anti-Inflammatory 15-Epi-Lipoxin A4 Production J. Immunol., September 1, 2008; 181(5): 3515 - 3523. [Abstract] [Full Text] [PDF]

				Y. Ye, J. D. Martinez, R. J. Perez-Polo, Y. Lin, B. F. Uretsky, and Y. Birnbaum The role of eNOS, iNOS, and NF-{kappa}B in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H343 - H351. [Abstract] [Full Text] [PDF]

				Y. Birnbaum, Y. Lin, Y. Ye, R. Merla, J. R. Perez-Polo, and B. F. Uretsky Pretreatment With High-Dose Statin, But Not Low-Dose Statin, Ezetimibe, or the Combination of Low-Dose Statin and Ezetimibe, Limits Infarct Size in the Rat Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2008; 13(1): 72 - 79. [Abstract] [PDF]

				S. Hong, T. F. Porter, Y. Lu, S. F. Oh, P. S. Pillai, and C. N. Serhan Resolvin E1 Metabolome in Local Inactivation during Inflammation-Resolution J. Immunol., March 1, 2008; 180(5): 3512 - 3519. [Abstract] [Full Text] [PDF]

				R. Merla, Y. Ye, Y. Lin, S. Manickavasagam, M.-H. Huang, R. J. Perez-Polo, B. F. Uretsky, and Y. Birnbaum The central role of adenosine in statin-induced ERK1/2, Akt, and eNOS phosphorylation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1918 - H1928. [Abstract] [Full Text] [PDF]

				Y. Ye, Y. Lin, R. Perez-Polo, M.-H. Huang, M. G. Hughes, D. J. McAdoo, S. Manickavasagam, B. F. Uretsky, and Y. Birnbaum Enhanced cardioprotection against ischemia-reperfusion injury with a dipyridamole and low-dose atorvastatin combination Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H813 - H818. [Abstract] [Full Text] [PDF]

				G. Salinas, U. C. Rangasetty, B. F. Uretsky, and Y. Birnbaum The Cycloxygenase 2 (COX-2) Story: It's Time to Explain, Not Inflame Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 98 - 111. [Abstract] [PDF]

				Y. Birnbaum, Y. Lin, Y. Ye, J. D. Martinez, M.-H. Huang, C. Y. Lui, J. R Perez-Polo, and B. F. Uretsky Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2891 - H2897. [Abstract] [Full Text] [PDF]

				M. Yano, T. Matsumura, T. Senokuchi, N. Ishii, Y. Murata, K. Taketa, H. Motoshima, T. Taguchi, K. Sonoda, D. Kukidome, et al. Statins Activate Peroxisome Proliferator-Activated Receptor {gamma} Through Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase-Dependent Cyclooxygenase-2 Expression in Macrophages Circ. Res., May 25, 2007; 100(10): 1442 - 1451. [Abstract] [Full Text] [PDF]

				I. G. E. Zarraga and E. R. Schwarz Coxibs and Heart Disease: What We Have Learned and What Else We Need to Know J. Am. Coll. Cardiol., January 2, 2007; 49(1): 1 - 14. [Abstract] [Full Text] [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]

				Y. Birnbaum, Y. Ye, Y. Lin, S. Y. Freeberg, S. P. Nishi, J. D. Martinez, M.-H. Huang, B. F. Uretsky, and J. R. Perez-Polo Augmentation of Myocardial Production of 15-Epi-Lipoxin-A4 by Pioglitazone and Atorvastatin in the Rat Circulation, August 29, 2006; 114(9): 929 - 935. [Abstract] [Full Text] [PDF]

				S. Atar, Y. Ye, Y. Lin, S. Y. Freeberg, S. P. Nishi, S. Rosanio, M.-H. Huang, B. F. Uretsky, J. R. Perez-Polo, and Y. Birnbaum Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2 Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1960 - H1968. [Abstract] [Full Text] [PDF]

				I. F. Benter, M. H. M. Yousif, J. T. Anim, C. Cojocel, and D. I. Diz Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H684 - H691. [Abstract] [Full Text] [PDF]

				E. Fosslien Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 347 - 385. [Abstract] [Full Text] [PDF]

				S. F. Jones and I. Power Editorial I: Postoperative NSAIDs and COX-2 inhibitors: cardiovascular risks and benefits Br. J. Anaesth., September 1, 2005; 95(3): 281 - 284. [Full Text] [PDF]

				U. Laufs and M. Bohm Cardiac effects of statins-advancements and open questions Cardiovasc Res, June 1, 2005; 66(3): 427 - 429. [Full Text] [PDF]

				C. L. Wainwright Statins-is there no end to their usefulness? Cardiovasc Res, February 1, 2005; 65(2): 296 - 298. [Full Text] [PDF]

Online ISSN 1755-3245 - Print ISSN 0008-6363

Copyright © 2009 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics