Cyclo-oxygenase-2 (COX-2) Expression at the Site of Recent Myocardial Infarction: Friend or Foe?

Overview

Journal Heart

Date 2004 Mar 17

PMID 15020525

Citations 22

Authors

A Abbate

D Santini

G G L Biondi-Zoccai

S Scarpa

F Vasaturo

G Liuzzo

R Bussani

F Silvestri

F Baldi

F Crea

L M Biasucci

A Baldi

Affiliations

Soon will be listed here.

Abstract

Background: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia.

Objective: To assess COX-2 expression at the site of recent myocardial infarction.

Methods: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10-60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation (TUNEL) and immunostaining for activated caspase-3.

Results: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates (median 17.9% (interquartile range 11.0-25.4%) v 3.7% (0.6-12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining (p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-alpha staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts (p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure (p = 0.035).

Conclusions: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause-effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.

Citing Articles

Effect of Li-ESWT on Testicular Tissue and Function in Androgen-Deficient Rat Model.

Tian W, Jeon S, Cho H, Ha U, Hong S, Lee J Oxid Med Cell Longev. 2022; 2022:5213573.

PMID: 35320975 PMC: 8938056. DOI: 10.1155/2022/5213573.

Cox-2 Antagonizes the Protective Effect of Sevoflurane on Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis through Inhibiting the Akt Pathway.

Guo C, Zhang L, Gao Y, Sun J, Fan L, Bai Y Dis Markers. 2021; 2021:4114593.

PMID: 34917200 PMC: 8670977. DOI: 10.1155/2021/4114593.

D-Tagatose Feeding Reduces the Risk of Sugar-Induced Exacerbation of Myocardial I/R Injury When Compared to Its Isomer Fructose.

Durante M, Sgambellone S, Lucarini L, Failli P, Laurino A, Collotta D Front Mol Biosci. 2021; 8:650962.

PMID: 33928123 PMC: 8076855. DOI: 10.3389/fmolb.2021.650962.

The Role of NLRP3 Inflammasome in Pericarditis: Potential for Therapeutic Approaches.

Mauro A, Bonaventura A, Vecchie A, Mezzaroma E, Carbone S, Narayan P JACC Basic Transl Sci. 2021; 6(2):137-150.

PMID: 33665514 PMC: 7907621. DOI: 10.1016/j.jacbts.2020.11.016.

LINC00528 regulates myocardial infarction by targeting the miR-143-3p/COX-2 axis.

Liu K, Zhao D, Wang D Bioengineered. 2019; 11(1):11-18.

PMID: 31833800 PMC: 6961595. DOI: 10.1080/21655979.2019.1704535.

References

Wong S, Fukuchi M, Melnyk P, Rodger I, Giaid A . Induction of cyclooxygenase-2 and activation of nuclear factor-kappaB in myocardium of patients with congestive heart failure. Circulation. 1998; 98(2):100-3. DOI: 10.1161/01.cir.98.2.100. View

Collaco-Moraes Y, Aspey B, Harrison M, de Belleroche J . Cyclo-oxygenase-2 messenger RNA induction in focal cerebral ischemia. J Cereb Blood Flow Metab. 1996; 16(6):1366-72. DOI: 10.1097/00004647-199611000-00035. View

Nogawa S, Zhang F, Ross M, Iadecola C . Cyclo-oxygenase-2 gene expression in neurons contributes to ischemic brain damage. J Neurosci. 1997; 17(8):2746-55. PMC: 6573095. View

Smith W, Garavito R, Dewitt D . Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem. 1996; 271(52):33157-60. DOI: 10.1074/jbc.271.52.33157. View

Takadera T, Yumoto H, Tozuka Y, Ohyashiki T . Prostaglandin E(2) induces caspase-dependent apoptosis in rat cortical cells. Neurosci Lett. 2002; 317(2):61-4. DOI: 10.1016/s0304-3940(01)02449-1. View

Govoni S, Masoero E, Favalli L, Rozza A, Scelsi R, Viappiani S . The Cycloxygenase-2 inhibitor SC58236 is neuroprotective in an in vivo model of focal ischemia in the rat. Neurosci Lett. 2001; 303(2):91-4. DOI: 10.1016/s0304-3940(01)01675-5. View

Semenza G . Surviving ischemia: adaptive responses mediated by hypoxia-inducible factor 1. J Clin Invest. 2000; 106(7):809-12. PMC: 381427. DOI: 10.1172/JCI11223. View

Shinmura K, Tang X, Wang Y, Xuan Y, Liu S, Takano H . Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits. Proc Natl Acad Sci U S A. 2000; 97(18):10197-202. PMC: 27805. DOI: 10.1073/pnas.97.18.10197. View

Saito T, Rodger I, Hu F, Shennib H, Giaid A . Inhibition of cyclooxygenase-2 improves cardiac function in myocardial infarction. Biochem Biophys Res Commun. 2000; 273(2):772-5. DOI: 10.1006/bbrc.2000.3010. View

10.

Saikumar P, Dong Z, Patel Y, Hall K, Hopfer U, Weinberg J . Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene. 1999; 17(26):3401-15. DOI: 10.1038/sj.onc.1202590. View

11.

LaPointe M, Isenovic E . Interleukin-1beta regulation of inducible nitric oxide synthase and cyclooxygenase-2 involves the p42/44 and p38 MAPK signaling pathways in cardiac myocytes. Hypertension. 1999; 33(1 Pt 2):276-82. DOI: 10.1161/01.hyp.33.1.276. View

12.

Nakayama M, Uchimura K, Zhu R, Nagayama T, Rose M, Stetler R . Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia. Proc Natl Acad Sci U S A. 1998; 95(18):10954-9. PMC: 28002. DOI: 10.1073/pnas.95.18.10954. View

13.

Abbate A, Biondi-Zoccai G, Bussani R, Dobrina A, Camilot D, Feroce F . Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure. J Am Coll Cardiol. 2003; 41(5):753-60. DOI: 10.1016/s0735-1097(02)02959-5. View

14.

Mani K, Kitsis R . Myocyte apoptosis: programming ventricular remodeling. J Am Coll Cardiol. 2003; 41(5):761-4. DOI: 10.1016/s0735-1097(02)02958-3. View

15.

Rocha R, Rudolph A, Frierdich G, Nachowiak D, Kekec B, Blomme E . Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol. 2002; 283(5):H1802-10. DOI: 10.1152/ajpheart.01096.2001. View

16.

Abbate A, Bussani R, Biondi-Zoccai G, Rossiello R, Silvestri F, Baldi F . Persistent infarct-related artery occlusion is associated with an increased myocardial apoptosis at postmortem examination in humans late after an acute myocardial infarction. Circulation. 2002; 106(9):1051-4. DOI: 10.1161/01.cir.0000030936.97158.c4. View

17.

Shinmura K, Xuan Y, Tang X, Kodani E, Han H, Zhu Y . Inducible nitric oxide synthase modulates cyclooxygenase-2 activity in the heart of conscious rabbits during the late phase of ischemic preconditioning. Circ Res. 2002; 90(5):602-8. DOI: 10.1161/01.res.0000012202.52809.40. View

18.

Baldi A, Abbate A, Bussani R, Patti G, Melfi R, Angelini A . Apoptosis and post-infarction left ventricular remodeling. J Mol Cell Cardiol. 2002; 34(2):165-74. DOI: 10.1006/jmcc.2001.1498. View

19.

Saito T, Rodger I, Shennib H, Hu F, Tayara L, Giaid A . Cyclooxygenase-2 (COX-2) in acute myocardial infarction: cellular expression and use of selective COX-2 inhibitor. Can J Physiol Pharmacol. 2003; 81(2):114-9. DOI: 10.1139/y03-023. View

20.

Zhang Z, Vezza R, Plappert T, McNamara P, Lawson J, Austin S . COX-2-dependent cardiac failure in Gh/tTG transgenic mice. Circ Res. 2003; 92(10):1153-61. DOI: 10.1161/01.RES.0000071749.22027.45. View