PMID- 12031703
OWN - NLM
STAT- MEDLINE
DCOM- 20020801
LR  - 20190513
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 54
IP  - 3
DP  - 2002 Jun
TI  - Intramyocardial injection of naked DNA encoding HIF-1alpha/VP16 hybrid to enhance 
      angiogenesis in an acute myocardial infarction model in the rat.
PG  - 576-83
AB  - OBJECTIVES: The therapeutic utility of hypoxia-inducible factor-1 (HIF-1) 
      transcriptional regulatory system for ischemic hindlimb has been demonstrated. It 
      is not yet known whether this transcriptional regulatory system can be used as a 
      therapeutic strategy to enhance collateral vessel formation in myocardial 
      tissues, where acute hypoxia occurs due to inadequate perfusion. We aimed to test 
      the hypothesis that exogenous administration of HIF-1alpha/VP16 could enhance 
      collateral vessel formation in a rat acute myocardial infarction model. METHODS: 
      Sprague-Dawley rats received ligation of the proximal left anterior descending 
      coronary artery to induce acute myocardial infarction. Immediately after the 
      ligation, 50 microg total plasmid DNA (control, plasmid encoding human vascular 
      endothelial growth factor (pVEGF(165)), or pHIF-1alpha/VP16) was injected into 
      the infarct area at three locations. RESULTS: Reverse transcription-polymerase 
      chain reaction (RT-PCR) showed the presence of HIF-1alpha and VEGF mRNA in the 
      myocardium, but not in other organs at days 3 and 7. The infarct size 
      significantly decreased from 37+/-4% (control) to 24+/-2% in the VEGF-treated 
      group and 23+/-2% in the HIF-1alpha/VP16 treated group (P<0.05). Capillary 
      density also significantly increased from 550+/-75/mm(2) (control) to 
      850+/-75/mm(2) in the VEGF group and 850+/-50/mm(2) in the 
      HIF-1alpha/VP16-treated group (P<0.01). Combined therapy with HIF-1alpha/VP16 and 
      VEGF resulted in higher capillary density (1230+/-50/mm(2)) than treatment with 
      either therapy alone. Regional myocardial blood flow was also higher in the 
      treated groups than in the control. Plasma levels of VEGF were also significantly 
      higher in the HIF-1alpha/VP16 and VEGF-treated group than in the control group. 
      CONCLUSIONS: The HIF-1alpha/VP16 hybrid transcription factor is able to reduce 
      infarct size and enhance neovascularization in an acute ischemic myocardium. The 
      potency of VEGF and HIF-1alpha/VP16 hybrid as therapeutic angiogenic factors in 
      acute hypoxic myocardium is similar.
FAU - Shyu, Kou Gi
AU  - Shyu KG
AD  - Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
FAU - Wang, Mei Ti
AU  - Wang MT
FAU - Wang, Bao Wei
AU  - Wang BW
FAU - Chang, Chih Chuna
AU  - Chang CC
FAU - Leu, Jyh Gang
AU  - Leu JG
FAU - Kuan, Peiliang
AU  - Kuan P
FAU - Chang, Hang
AU  - Chang H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Capillaries
MH  - Collateral Circulation
MH  - DNA/*administration & dosage
MH  - Endothelial Growth Factors/genetics
MH  - *Etoposide
MH  - Gene Expression
MH  - Genetic Therapy/*methods
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Injections
MH  - Lymphokines/genetics
MH  - Male
MH  - Models, Animal
MH  - Myocardial Infarction/*therapy
MH  - Myocardium/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factors/*genetics
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2002/05/29 10:00
MHDA- 2002/08/02 10:01
CRDT- 2002/05/29 10:00
PHST- 2002/05/29 10:00 [pubmed]
PHST- 2002/08/02 10:01 [medline]
PHST- 2002/05/29 10:00 [entrez]
AID - S0008636302002596 [pii]
AID - 10.1016/s0008-6363(02)00259-6 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2002 Jun;54(3):576-83. doi: 10.1016/s0008-6363(02)00259-6.