Density dependent expression of PDGF-A modulates the angiotensin II dependent proliferation of rat cardiac fibroblasts.
The proliferative effect of angiotensin II (Ang-II) on primary cardiac fibroblasts is not well understood and controversially discussed. Results described here show that fibroblasts from adult rat hearts exhibit a cell density dependent Ang-II induced cell proliferation. Whereas we could not detect a proliferative effect of Ang-II on confluent cells, which are still able to divide as shown by stimulation with platelet derived growth factor (PDGF), we observed an Ang-II induced cell division of approximately 20 % in non-confluent cells. At both densities, signal transduction molecules such as the mitogen activated protein kinases (MAPK) are activated. There has been substantial evidence that Ang-II may induce the expression and secretion of several growth factors. We demonstrated an approximately fivefold increase in platelet derived growth factor-A (PDGF-A) chain and transforming growth factor beta1 (TGF-beta1) mRNA-expression within non-confluent cardiac fibroblasts by semiquantitative reverse polymerase chain reaction, RT-PCR. In contrast, the mRNA-expression of basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), PDGF-A/-B chains, and TGF-beta1 remained unchanged within confluent cardiac fibroblasts. Experiments with neutralizing antibodies showed that PDGF-AA is an important growth factor regulating cell proliferation, whereas TGF-beta1 interferes with cell size regulation. In summary, we could show that the Ang-II induced cell proliferation in adult cardiac fibroblasts is mainly due to cell density dependent expression of growth factors like PDGF-AA.
Simm
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A
Institut für klinische Biochemie und Pathobiochemie, Würzburg, Germany. simm@klin-biochem.uni-wuerzburg.de
Diez
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C
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D000804:Angiotensin II