Circulation Research, Vol 65, 671-683, Copyright © 1989 by American Heart Association

ARTICLES

Arachidonate metabolism in cultured fibroblasts derived from normal and infarcted canine heart

DR Weber, ED Stroud and SM Prescott
Nora Eccles Harrison Cardiovascular Research, University of Utah, Salt Lake City 84112.

Metabolites of arachidonic acid (eicosanoids) may have an important role in the healing process after myocardial infarction. We examined the ability of cardiac fibroblasts from normal and from healing infarcted ventricle to metabolize arachidonate. We induced myocardial infarction in dogs and then allowed them to recover for 1 week, at which time they were killed, and the heart was removed. Fibroblasts were harvested from normal and from the healing, infarcted areas of the left ventricle. The cells from each source were morphologically indistinguishable. There were 347 +/- 102-fold more fibroblasts cultured from the infarcted area than from the normal area. Interestingly, the infarct-derived cells had a slower doubling time (37.4 +/- 3.7 hours) than the normal cells (22.0 +/- 3.6 hours). The uptake of exogenous arachidonate and its distribution in complex lipids was the same in the cells from each area. When stimulated with the calcium ionophore, free exogenous arachidonate, bradykinin, or histamine the cells produced prostaglandin E2 and prostaglandin I2. In each case the infarct-derived cells produced from twofold to fivefold more prostaglandin than the normal cells. We also found that prostaglandin synthesis was highly dependent on the growth state of the cells with a marked decrease a confluence. Finally, in experiments designed to mimic the early state of infarction, we confirmed that isolated cardiac myocytes release arachidonate and showed that normal fibroblasts can incorporate it. The production of eicosanoids by cardiac fibroblasts may be substantial during the healing of myocardial infarction due to their dramatic proliferation and the increased prostaglandin production per cell.

This article has been cited by other articles:

				S. Ichihara, T. Senbonmatsu, E. Price Jr, T. Ichiki, F. A. Gaffney, and T. Inagami Targeted Deletion of Angiotensin II Type 2 Receptor Caused Cardiac Rupture After Acute Myocardial Infarction Circulation, October 22, 2002; 106(17): 2244 - 2249. [Abstract] [Full Text] [PDF]

				T. Tsuruda, M. Jougasaki, G. Boerrigter, B. K. Huntley, H. H. Chen, A. B. D'Assoro, S. C. Lee, A. M. Larsen, A. Cataliotti, and J. C. Burnett Jr Cardiotrophin-1 Stimulation of Cardiac Fibroblast Growth: Roles for Glycoprotein 130/Leukemia Inhibitory Factor Receptor and the Endothelin Type A Receptor Circ. Res., February 8, 2002; 90(2): 128 - 134. [Abstract] [Full Text] [PDF]

				M. Mendez and M. C. LaPointe Trophic Effects of the Cyclooxygenase-2 Product Prostaglandin E2 in Cardiac Myocytes Hypertension, February 1, 2002; 39(2): 382 - 388. [Abstract] [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]

				A. M. Gallagher, H. Yu, and M. P. Printz Bradykinin-Induced Reductions in Collagen Gene Expression Involve Prostacyclin Hypertension, July 1, 1998; 32(1): 84 - 88. [Abstract] [Full Text] [PDF]

				K. T. Weber Extracellular Matrix Remodeling in Heart Failure : A Role for De Novo Angiotensin II Generation Circulation, December 2, 1997; 96(11): 4065 - 4082. [Full Text]

				J. W. Adams, D. S. Migita, M. K. Yu, R. Young, M. S. Hellickson, F. E. Castro-Vargas, J. D. Domingo, P. H. Lee, J. S. Bui, and S. A. Henderson Prostaglandin F[IMAGE] Stimulates Hypertrophic Growth of Cultured Neonatal Rat Ventricular Myocytes J. Biol. Chem., January 12, 1996; 271(2): 1179 - 1186. [Abstract] [Full Text] [PDF]

				T. Tsuruda, M. Jougasaki, G. Boerrigter, B. K. Huntley, H. H. Chen, A. B. D'Assoro, S. C. Lee, A. M. Larsen, A. Cataliotti, and J. C. Burnett Jr Cardiotrophin-1 Stimulation of Cardiac Fibroblast Growth: Roles for Glycoprotein 130/Leukemia Inhibitory Factor Receptor and the Endothelin Type A Receptor Circ. Res., February 8, 2002; 90(2): 128 - 134. [Abstract] [Full Text] [PDF]

				M. Takeda, Y. Kagaya, J. Takahashi, T. Sugie, J. Ohta, J. Watanabe, K. Shirato, H. Kondo, and K. Goto Gene Expression and In Situ Localization of Diacylglycerol Kinase Isozymes in Normal and Infarcted Rat Hearts: Effects of Captopril Treatment Circ. Res., August 3, 2001; 89(3): 265 - 272. [Abstract] [Full Text] [PDF]