AJP - Heart and Circulatory Physiology, Vol 271, Issue 6 2197-H2208, Copyright © 1996 by American Physiological Society

ARTICLES

Prostaglandin F2 alpha induces cardiac myocyte hypertrophy in vitro and cardiac growth in vivo

J. Lai, H. Jin, R. Yang, J. Winer, W. Li, R. Yen, K. L. King, F. Zeigler, A. Ko, J. Cheng, S. Bunting and N. F. Paoni
Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080, USA.

Several prostaglandins [prostaglandin (PG) A2, -B2, -D2, -E2, -F2 alpha, and -I2 and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the ability to induce hypertrophy of rat neonatal cardiac ventricular myocytes. Myocyte hypertrophy was induced specifically by PGF2 alpha. Myocytes exposed to this prostanoid in culture increased in size and protein content. The contractile fibrils within the cells became organized into parallel arrays, and the cells tended to cluster and beat spontaneously. PGF2 alpha also induced the expression of c-fos, atrial natriuretic factor (ANF), and alpha-skeletal actin in these cells. The effects of PGF2 alpha were compared with several known cardiac myocyte hypertrophy factors (phenylephrine, endothelin-1, leukemia inhibitory factor, cardiotrophin-1, and angiotensin II). PGF2 alpha was found to be intermediate in potency among the factors but induced a level of ANF production that was approximately 10-fold higher than any of the other effectors. Responsiveness to PGF2 alpha was not limited to neonatal cardiocytes. Ventricular myocytes isolated from adult rats also responded specifically to PGF2 alpha with a morphological change similar to that observed with phenylephrine and by producing ANF. In rats, chronic administration of fluprostenol, a potent agonist analogue of PGF2 alpha, resulted in a dose-dependent increase in heart weight- and ventricular weight-to-body weight ratios. The amount of PGF2 alpha extractable from the hearts of rats with cardiac hypertrophy induced by myocardial infarction was also found to be greater than that in sham-operated control rats. These results indicate that PGF2 alpha may play an important role in inducing cardiac hypertrophy.

This article has been cited by other articles:

				K. M. A. O'Reilly, R. P. Phipps, T. H. Thatcher, B. A. Graf, J. Van Kirk, and P. J. Sime Crystalline and amorphous silica differentially regulate the cyclooxygenase-prostaglandin pathway in pulmonary fibroblasts: implications for pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1010 - L1016. [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 Mitra, B Chang, and T James Drug points: Exacerbation of angina associated with latanoprost BMJ, October 6, 2001; 323(7316): 783 - 783. [Full Text] [PDF]

				R. Schuette and M. C. LaPointe Phorbol ester stimulates cyclooxygenase-2 expression and prostanoid production in cardiac myocytes Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H719 - H725. [Abstract] [Full Text] [PDF]

				K. L. Pierce, H. Fujino, D. Srinivasan, and J. W. Regan Activation of FP Prostanoid Receptor Isoforms Leads to Rho-mediated Changes in Cell Morphology and in the Cell Cytoskeleton J. Biol. Chem., December 10, 1999; 274(50): 35944 - 35949. [Abstract] [Full Text] [PDF]

				P. H. Sugden Signaling in Myocardial Hypertrophy : Life After Calcineurin? Circ. Res., April 2, 1999; 84(6): 633 - 646. [Full Text] [PDF]

				A. Sebkhi, L. Zhao, L. Lu, C. S. Haley, D. J. R. Nunez, and M. R. Wilkins Genetic Determination of Cardiac Mass in Normotensive Rats : Results From an F344WKY Cross Hypertension, April 1, 1999; 33(4): 949 - 953. [Abstract] [Full Text] [PDF]

				P. Kunapuli, J. A. Lawson, J. A. Rokach, J. L. Meinkoth, and G. A. FitzGerald Prostaglandin F2alpha (PGF2alpha ) and the Isoprostane, 8,12-iso-Isoprostane F2alpha -III, Induce Cardiomyocyte Hypertrophy. DIFFERENTIAL ACTIVATION OF DOWNSTREAM SIGNALING PATHWAYS J. Biol. Chem., August 28, 1998; 273(35): 22442 - 22452. [Abstract] [Full Text] [PDF]

				J. W. Adams, V. P. Sah, S. A. Henderson, and J. H. Brown Tyrosine Kinase and c-Jun NH2-Terminal Kinase Mediate Hypertrophic Responses to Prostaglandin F2{alpha} in Cultured Neonatal Rat Ventricular Myocytes Circ. Res., July 27, 1998; 83(2): 167 - 178. [Abstract] [Full Text] [PDF]

				D. M. Hwang, A. A. Dempsey, R.-X. Wang, M. Rezvani, J. D. Barrans, J. D. MHSc, K.-S. Dai, H.-Y. Wang, H. Ma, E. Cukerman, et al. A Genome-Based Resource for Molecular Cardiovascular Medicine : Toward a Compendium of Cardiovascular Genes Circulation, December 16, 1997; 96(12): 4146 - 4203. [Abstract] [Full Text]