title: Expression and localization of platelet-derived growth factor ligand and receptor protein during acute and chronic rejection of rat cardiac allografts.
abstract: 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 alpha and R beta) proteins during acute and chronic rejection.
  
  
  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-R beta 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 alpha-smooth muscle actin-positive but also alpha-smooth muscle actin-negative myofibroblast-like cells and to a lesser extent, ED1-immunoreactive cells. Both PDGF-R alpha and -R beta 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 alpha expression in intimal cells. Furthermore, linear regression analysis revealed that PDGF-AA, PDGF-R alpha, and PDGF-R beta 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.
authors.affiliation: Transplantation Laboratory, University of Helsinki, and Helsinki University Central Hospital, Finland. Karl.Lemstrom@Helsinki.Fi
authors.forename: K B
authors.initials: KB
authors.lastname: Lemström
authors.forename: P K
authors.initials: PK
authors.lastname: Koskinen
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D007165:Immunosuppression Therapy; D008024:Ligands; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000378:metabolism*
chemical_list: D008024:Ligands; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor