PMID- 23331861
OWN - NLM
STAT- MEDLINE
DCOM- 20130815
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Linking)
VI  - 13
IP  - 3
DP  - 2013 Mar
TI  - Differential effects of pharmacological HIF preconditioning of donors versus 
      recipients in rat cardiac allografts.
PG  - 600-10
LID - 10.1111/ajt.12064 [doi]
AB  - Ischemia-reperfusion injury (IRI) induces hypoxia-inducible factor-1 (HIF-1) in 
      the myocardium, but the consequences remain elusive. We investigated HIF-1 
      activation during cold and warm ischemia and IRI in rat hearts and cardiac 
      syngrafts. We also tested the effect of HIF-alpha stabilizing prolyl hydroxylase 
      inhibitor (FG-4497) on IRI or allograft survival. Ex vivo ischemia of the heart 
      increased HIF-1alpha expression in a time- and temperature-dependent fashion. 
      Immunohistochemistry localized HIF-1alpha to all cardiac cell types. After 
      reperfusion, HIF-1alpha immunoreactivity persisted in smooth muscle cells and 
      cardiomyocytes in the areas with IRI. This was accompanied with a transient 
      induction of protective HIF-1 downstream genes. Donor FG-4497 pretreatment for 4 
      h enhanced IRI in cardiac allografts as evidenced by an increase in cardiac 
      troponin T release, cardiomyocyte apoptosis, and activation of innate immunity. 
      Recipient FG-4497 pretreatment for 4 h decreased infiltration of ED1(+) 
      macrophages, and mildly improved the long-term allograft survival. In syngrafts 
      donor FG-4497 pretreatment increased activation of innate immunity, but did not 
      induce myocardial damage. We conclude that the HIF-1 pathway is activated in 
      heart transplants. We suggest that pharmacological HIF-alpha preconditioning of 
      cardiac allografts donors would not lead to clinical benefit, while in recipients 
      it may result in antiinflammatory effects and prolonged allograft survival.
CI  - (c) Copyright 2013 The American Society of Transplantation and the American Society 
      of Transplant Surgeons.
FAU - Keranen, M A I
AU  - Keranen MA
AD  - Transplantation Laboratory, Haartman Institute, University of Helsinki and 
      HUSLAB, Helsinki University Central Hospital, Helsinki, Finland.
FAU - Tuuminen, R
AU  - Tuuminen R
FAU - Syrjala, S
AU  - Syrjala S
FAU - Krebs, R
AU  - Krebs R
FAU - Walkinshaw, G
AU  - Walkinshaw G
FAU - Flippin, L A
AU  - Flippin LA
FAU - Arend, M
AU  - Arend M
FAU - Koskinen, P K
AU  - Koskinen PK
FAU - Nykanen, A I
AU  - Nykanen AI
FAU - Lemstrom, K B
AU  - Lemstrom KB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130117
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Biomarkers)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Biomarkers/analysis
MH  - Enzyme Inhibitors/*pharmacology
MH  - Heart/*physiopathology
MH  - *Heart Transplantation
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Inflammation/diagnosis/metabolism
MH  - *Ischemic Preconditioning
MH  - Macrophages/metabolism/pathology
MH  - Male
MH  - Myocytes, Cardiac/drug effects/pathology
MH  - Procollagen-Proline Dioxygenase/*antagonists & inhibitors
MH  - Rats
MH  - Rats, Inbred WF
MH  - Reperfusion Injury/metabolism/pathology/*prevention & control
MH  - Transplantation, Homologous
EDAT- 2013/01/22 06:00
MHDA- 2013/08/16 06:00
CRDT- 2013/01/22 06:00
PHST- 2012/04/17 00:00 [received]
PHST- 2012/11/08 00:00 [revised]
PHST- 2012/11/08 00:00 [accepted]
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/08/16 06:00 [medline]
AID - S1600-6135(22)25849-3 [pii]
AID - 10.1111/ajt.12064 [doi]
PST - ppublish
SO  - Am J Transplant. 2013 Mar;13(3):600-10. doi: 10.1111/ajt.12064. Epub 2013 Jan 17.