title: Hypertension increases expression of growth factors and MHC II in chronic allograft nephropathy.
abstract: BACKGROUND
  Hypertension of the recipient is strongly associated with chronic allograft nephropathy. It is unclear, however, whether hypertension is the cause or the consequence of chronic allograft nephropathy.
  
  
  METHODS
  The present study was performed in the Fisher to Lewis rat kidney transplant model. Transplanted rats (N = eight in each group) received either no treatment or were made hypertensive by administration of deoxycorticosteron acetate (DOCA) and salt. Proteinuria and systolic blood pressure was measured monthly, grafts were harvested at 3 and 6 months for semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and for immunohistology.
  
  
  RESULTS
  Systolic blood pressure was markedly elevated in rats receiving DOCA/salt. Allografts of hypertensive animals contained significantly more cells expressing the proliferating cell nuclear antigen compared to isografts and to allografts from normotensive animals (P < 0.05). Histologic staining and mRNA expression of major histocompatibility complex (MHC) II was markedly increased in allografts of hypertensive animals compared to all other groups (P < 0.05). Expression of mRNA for platelet-derived growth factor-B (PDGF-B), transforming growth factor-beta (TGF-beta) and collagen was higher in allografts than in isografts and was highest in hypertensive animals.
  
  
  CONCLUSIONS
  We conclude that hypertension augments the expression of growth factors in the allograft possibly aggravating the intimal hyperplasia observed in chronic allograft nephropathy. By increasing the expression of MHC II antigens, hypertension may render the allograft more susceptible to alloantigen-dependent damage. Hypertension and alloantigen-dependent factors appear to exert additive or synergistic effects on inflammatory pathways leading to graft injury.
authors.affiliation: Department of Nephrology and Internal Intensive Care Medicine, Universitätsklinikum Charité, Campus Virchow Klinikum, Humboldt University, Berlin, Germany. ralf.schindler@charite.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Schindler
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Tullius
authors.forename: Yakup
authors.initials: Y
authors.lastname: Tanriver
authors.forename: Kerstin
authors.initials: K
authors.lastname: Noack
authors.forename: Ye
authors.initials: Y
authors.lastname: Qun
authors.forename: Jan-Steffen
authors.initials: JS
authors.lastname: Jürgensen
authors.forename: Ulrich
authors.initials: U
authors.lastname: Frei
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002908:Chronic Disease; D003900:Desoxycorticosterone; D015870:Gene Expression; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006977:Hypertension, Renal / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D016030:Kidney Transplantation; D008297:Male; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014184:Transplantation, Homologous
chemical_list: D000949:Histocompatibility Antigens Class II; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003900:Desoxycorticosterone