PMID- 17175275
OWN - NLM
STAT- MEDLINE
DCOM- 20070430
LR  - 20061218
IS  - 0041-1345 (Print)
IS  - 0041-1345 (Linking)
VI  - 38
IP  - 10
DP  - 2006 Dec
TI  - Effect of graft preservation and acute rejection on hypoxia-inducible factor-1 in 
      rat cardiac allografts.
PG  - 3372-3
AB  - Hypoxia plays an integral part in cardiac transplantation as prolonged graft 
      preservation is an individual risk factor for the development of cardiac 
      allograft vasculopathy (CAV). In this study we characterized the role of 
      hypoxia-inducible factor-1 (HIF-1) during prolonged graft preservation, 
      ischemia-reperfusion (I/R), acute rejection, and chronic rejection. Heart 
      transplantations were performed from Dark Agouti (DA) to Wister-Furth (allo) or 
      DA to DA (syn) rats, without immunosuppression (acute rejection model, harvested 
      at day 5) or with cyclosporine (chronic rejection model, harvested at day 60). To 
      study the effect of preservation on HIF-1 regulation, normal DA hearts were 
      subjected to different cold ischemia times with or without 45 minutes of 
      additional warm ischemia. The role of I/R was studied by harvesting syngrafts at 
      different time points after reperfusion. Real-time reverse-transcriptase 
      polymerase chain reaction quantified total HIF-1 mRNA, while enzyme-linked 
      immunosorbent assay and immunohistochemistry quantified and localized HIF-1 
      protein. Our results show that HIF-1 nuclear immunoreactivity is increased during 
      graft preservation and I/R leads to loss of nuclear HIF-1 immunoreactivity. Acute 
      rejection induced HIF-1 in mRNA level. Our findings thus indicated that HIF-1 is 
      activated during transplantation and suggested that manipulation of the HIF-1 
      pathway might reveal new therapeutic options to manage CAV.
FAU - Keranen, M A I
AU  - Keranen MA
AD  - Transplantation Laboratory, University of Helsinki and Helsinki University 
      Central Hospital, Helsinki, Finland.
FAU - Nykanen, A I
AU  - Nykanen AI
FAU - Krebs, R
AU  - Krebs R
FAU - Tuuminen, R
AU  - Tuuminen R
FAU - Sandelin, H
AU  - Sandelin H
FAU - Koskinen, P K
AU  - Koskinen PK
FAU - Lemstrom, K B
AU  - Lemstrom KB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Hypoxia-Inducible Factor 1)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia
MH  - Gene Expression Regulation
MH  - Graft Rejection/*physiopathology
MH  - Heart Transplantation/immunology/*physiology
MH  - Hypoxia-Inducible Factor 1/*genetics
MH  - Immunohistochemistry
MH  - Organ Preservation
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Rats, Inbred WF
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transplantation, Homologous
MH  - Transplantation, Isogeneic
EDAT- 2006/12/19 09:00
MHDA- 2007/05/01 09:00
CRDT- 2006/12/19 09:00
PHST- 2006/07/26 00:00 [received]
PHST- 2006/12/19 09:00 [pubmed]
PHST- 2007/05/01 09:00 [medline]
PHST- 2006/12/19 09:00 [entrez]
AID - S0041-1345(06)01286-3 [pii]
AID - 10.1016/j.transproceed.2006.10.057 [doi]
PST - ppublish
SO  - Transplant Proc. 2006 Dec;38(10):3372-3. doi: 10.1016/j.transproceed.2006.10.057.