Arachidonate metabolism in cultured fibroblasts derived from normal and infarcted canine heart.
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.
Weber
D R
DR
Nora Eccles Harrison Cardiovascular Research, University of Utah, Salt Lake City 84112.
Stroud
E D
ED
Prescott
S M
SM
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D004285:Dogs; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D008854:Microscopy, Electron; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D011453:Prostaglandins / Q000096:biosynthesis; D012016:Reference Values
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D000001:Calcimycin