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(Circulation. 1997;96:1240-1249.)
© 1997 American Heart Association, Inc.

Articles

Expression and Localization of Platelet-Derived Growth Factor Ligand and Receptor Protein During Acute and Chronic Rejection of Rat Cardiac Allografts

Karl B. Lemström, MD, PhD; ; Petri K. Koskinen, MD, PhD

From the Transplantation Laboratory, University of Helsinki, and Helsinki University Central Hospital, Finland.

Correspondence to Dr Karl Lemström, Transplantation Laboratory, PO Box 21 (Haartmaninkatu 3), FIN-00014 University of Helsinki, Finland. E-mail Karl.Lemstrom{at}Helsinki.Fi

Background The molecular mechanisms of cardiac allograft vasculopathy (CAV) remain largely unknown. Using rat cardiac allografts, we examined by immunohistochemistry the expression and localization of platelet-derived growth factor ligand (PDGF-AA and -BB) and receptor (R and Rß) proteins during acute and chronic rejection.

Methods and Results In acute rejection, a prominent induction of both PDGF ligand and receptor proteins occurred in the interstitial mononuclear inflammatory cells (P<.05), most of which were ED1-immunoreactive. PDGF-Rß was also induced in the capillary endothelium (P<.01). In cardiac allografts with severe intimal thickening, PDGF-AA expression was localized to the media and intima, whereas PDGF-BB expression was less prominent and was detected mainly in interstitial ED1-immunoreactive inflammatory cells. Double staining revealed that intimal cells expressing PDGF-AA were -smooth muscle actin–positive but also -smooth muscle actin–negative myofibroblast-like cells and to a lesser extent, ED1-immunoreactive cells. Both PDGF-R and -Rß expression occurred in intimal, arterial endothelial, and interstitial mononuclear inflammatory cells. High-dose cyclosporin A (CsA) treatment significantly reduced both PDGF-AA and PDGF-R expression in intimal cells. Furthermore, linear regression analysis revealed that PDGF-AA, PDGF-R, and PDGF-Rß expression in intimal cells and PDGF-BB expression in interstitial mononuclear inflammatory cells correlated with intimal thickening.

Conclusions Alloimmune injury induces the expression of PDGF ligands, especially of PDGF-AA, in the graft vasculature and sufficient immunosuppression with CsA suppresses the expression of PDGF and inhibits the development of CAV. PDGF may have a substantial role in the regulation of smooth muscle cell migration and proliferation in an autocrine or paracrine manner during the development of CAV.

Key Words: transplantation • immunohistochemistry • arteriosclerosis

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