This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mendez, M. Articles by LaPointe, M. C. Search for Related Content PubMed PubMed Citation Articles by Mendez, M. Articles by LaPointe, M. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Cell signalling/signal transduction Hypertrophy Physiological and pathological control of gene expression

(Hypertension. 2002;39:382.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Trophic Effects of the Cyclooxygenase-2 Product Prostaglandin E₂ in Cardiac Myocytes

Mariela Mendez; Margot C. LaPointe

From the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich.

Correspondence to Margot C. LaPointe, PhD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202-2689. E-mail mclapointe{at}aol.com

Interleukin-1ß (IL-1ß), a proinflammatory cytokine, induces cyclooxygenase-2 (COX-2) in cultured neonatal ventricular myocytes (NVMs), resulting in the preferential production of prostaglandin E₂ (PGE₂). To explain the preferential PGE₂ release by myocytes, we studied whether its specific synthase, PGE₂ synthase (PGES), is also induced by IL-1ß. Because COX-2 has been extensively associated with cell growth, we questioned whether PGE₂ plays a role in cardiac cell growth. IL-1ß–treated myocytes showed induction of PGES protein and mRNA by Western blot and reverse transcription–polymerase chain reaction, respectively. Immunofluorescence studies revealed perinuclear localization of COX-2 and PGES in IL-1ß–treated myocytes. Exogenous PGE₂ increased protein synthesis in NVMs, as indicated by a 1.6-fold increase in [³H]leucine incorporation, comparable to the known hypertrophic factor phenylephrine (1.6-fold). Because PGE₂ exerts different effects through 4 receptor subtypes (EP₁, EP₂, EP₃, and EP₄), we investigated whether these receptors are functional in myocytes. Treatment of NVMs with the selective EP₁/EP₃ agonist sulprostone significantly increased protein synthesis (1.7-fold), whereas the EP₁/EP₂ antagonist AH6809 blocked this effect by 43%. In contrast, AH6809 had no effect on PGE₂-induced protein synthesis. Regarding second messengers, sulprostone had no effect on cAMP, whereas PGE₂ increased it. We concluded that (1) PGE₂ production requires the induction of its specific synthase; (2) in myocytes, the inducible enzymes COX-2 and PGES are perinuclear; and (3) PGE₂ and sulprostone induce cardiac myocyte growth but seem to activate a different subset of EP receptors.

Key Words: prostaglandins • hypertrophy, cardiac • receptors • myocytes

This article has been cited by other articles:

				N. Yoshikawa, M. Nagasaki, M. Sano, S. Tokudome, K. Ueno, N. Shimizu, S. Imoto, S. Miyano, M. Suematsu, K. Fukuda, et al. Ligand-based gene expression profiling reveals novel roles of glucocorticoid receptor in cardiac metabolism Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1363 - E1373. [Abstract] [Full Text] [PDF]

				J. Meyer-Kirchrath, M. Martin, C. Schooss, C. Jacoby, U. Flogel, A. Marzoll, J. W. Fischer, J. Schrader, K. Schror, and T. Hohlfeld Overexpression of prostaglandin EP3 receptors activates calcineurin and promotes hypertrophy in the murine heart Cardiovasc Res, February 1, 2009; 81(2): 310 - 318. [Abstract] [Full Text] [PDF]

				N. Degousee, S. Fazel, D. Angoulvant, E. Stefanski, S.-C. Pawelzik, M. Korotkova, S. Arab, P. Liu, T. F. Lindsay, S. Zhuo, et al. Microsomal Prostaglandin E2 Synthase-1 Deletion Leads to Adverse Left Ventricular Remodeling After Myocardial Infarction Circulation, April 1, 2008; 117(13): 1701 - 1710. [Abstract] [Full Text] [PDF]

				J.-Y. Qian, P. Harding, Y. Liu, E. Shesely, X.-P. Yang, and M. C. LaPointe Reduced Cardiac Remodeling and Function in Cardiac-Specific EP4 Receptor Knockout Mice With Myocardial Infarction Hypertension, February 1, 2008; 51(2): 560 - 566. [Abstract] [Full Text] [PDF]

				M. Testa, B. Rocca, L. Spath, F. O. Ranelletti, G. Petrucci, G. Ciabattoni, F. Naro, S. Schiaffino, M. Volpe, and C. Reggiani Expression and activity of cyclooxygenase isoforms in skeletal muscles and myocardium of humans and rodents J Appl Physiol, October 1, 2007; 103(4): 1412 - 1418. [Abstract] [Full Text] [PDF]

				M. M. Bamman Take two NSAIDs and call on your satellite cells in the morning J Appl Physiol, August 1, 2007; 103(2): 415 - 416. [Full Text] [PDF]

				N. Degousee, D. Angoulvant, S. Fazel, E. Stefanski, S. Saha, K. Iliescu, T. F. Lindsay, J. E. Fish, P. A. Marsden, R.-K. Li, et al. c-Jun N-terminal Kinase-mediated Stabilization of Microsomal Prostaglandin E2 Synthase-1 mRNA Regulates Delayed Microsomal Prostaglandin E2 Synthase-1 Expression and Prostaglandin E2 Biosynthesis by Cardiomyocytes J. Biol. Chem., June 16, 2006; 281(24): 16443 - 16452. [Abstract] [Full Text] [PDF]

				J.-Y. Qian, A. Leung, P. Harding, and M. C. LaPointe PGE2 stimulates human brain natriuretic peptide expression via EP4 and p42/44 MAPK Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1740 - H1746. [Abstract] [Full Text] [PDF]

				K. Shinmura, K. Tamaki, T. Sato, H. Ishida, and R. Bolli Prostacyclin attenuates oxidative damage of myocytes by opening mitochondrial ATP-sensitive K+ channels via the EP3 receptor Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2093 - H2101. [Abstract] [Full Text] [PDF]

				M. Mendez and M. C. LaPointe PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2111 - H2117. [Abstract] [Full Text] [PDF]

				G. Giannico, M. Mendez, and M. C. LaPointe Regulation of the membrane-localized prostaglandin E synthases mPGES-1 and mPGES-2 in cardiac myocytes and fibroblasts Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H165 - H174. [Abstract] [Full Text] [PDF]

				M. C. LaPointe, M. Mendez, A. Leung, Z. Tao, and X.-P. Yang Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in the mouse Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1416 - H1424. [Abstract] [Full Text] [PDF]

				M. Mendez and M. C. LaPointe PPAR{gamma} Inhibition of Cyclooxygenase-2, PGE2 Synthase, and Inducible Nitric Oxide Synthase in Cardiac Myocytes Hypertension, October 1, 2003; 42(4): 844 - 850. [Abstract] [Full Text] [PDF]

				J. Sadoshima Novel AT1 Receptor-Independent Functions of Losartan Circ. Res., April 19, 2002; 90(7): 754 - 756. [Full Text] [PDF]