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(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

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