PMID- 17264168
OWN - NLM
STAT- MEDLINE
DCOM- 20070530
LR  - 20201209
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 21
IP  - 7
DP  - 2007 May
TI  - VEGF-induced heme oxygenase-1 confers cytoprotection from lethal hyperoxia in 
      vivo.
PG  - 1422-32
AB  - Prolonged exposure to hyperoxia results in hyperoxic acute lung injury (HALI). 
      Vascular endothelial growth factor (VEGF) has been shown to have cytoprotective 
      effects and prolong survival in an in vivo model of HALI. Heme oxygenase-1 (HO-1) 
      has protective effects in hyperoxia; therefore, we hypothesized that induction of 
      HO-1 would be an important contributor to VEGF-induced cytoprotection. Using 
      inducible, lung-specific VEGF overexpressing transgenic mice, we demonstrated 
      that VEGF is a potent inducer of HO-1 mRNA and protein in mouse lung. To evaluate 
      the effect of inhibition of HO-1 on injury, VEGF transgenic mice were treated 
      with HO-1 short interfering RNA (HO-1 siRNA) and exposed to hyperoxia. Total lung 
      lavage protein concentration, TUNEL staining, lipid peroxidation, and wet-to-dry 
      ratio were all increased, consistent with increased injury. These findings were 
      corroborated by survival studies in which inhibition of HO-1 function using 
      tin-protoporphryin or silencing of HO-1 with lentiviral HO-1 short hairpin RNA 
      (ShRNA) significantly decreased survival in hyperoxia. We conclude from these 
      data that VEGF-induced HO-1 is an important contributor to cytoprotection in this 
      in vivo model of acute lung injury and that alterations in VEGF function in the 
      lung are likely to be important determinants of the outcome of acute lung injury.
FAU - Siner, Jonathan M
AU  - Siner JM
AD  - Section of Pulmonary and Critical Care Medicine, Yale University School of 
      Medicine, P.O. Box 208057, New Haven, CT 06520-8057, USA.
FAU - Jiang, Ge
AU  - Jiang G
FAU - Cohen, Zaza I
AU  - Cohen ZI
FAU - Shan, Peiying
AU  - Shan P
FAU - Zhang, Xuchen
AU  - Zhang X
FAU - Lee, Chun Geun
AU  - Lee CG
FAU - Elias, Jack A
AU  - Elias JA
FAU - Lee, Patty J
AU  - Lee PJ
LA  - eng
GR  - 5 F32 HL078127/HL/NHLBI NIH HHS/United States
GR  - R01 HL071595/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070130
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (DNA Primers)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bronchoalveolar Lavage Fluid
MH  - *Cytoprotection
MH  - DNA Primers
MH  - Disease Models, Animal
MH  - Enzyme Induction
MH  - Heme Oxygenase (Decyclizing)/*biosynthesis/genetics
MH  - Humans
MH  - Hyperoxia/enzymology/*prevention & control
MH  - In Situ Nick-End Labeling
MH  - Lipid Peroxidation
MH  - Lung/enzymology
MH  - Mice
MH  - Mice, Transgenic
MH  - RNA, Small Interfering
MH  - Respiratory Distress Syndrome/enzymology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor A/*physiology
EDAT- 2007/02/01 09:00
MHDA- 2007/05/31 09:00
CRDT- 2007/02/01 09:00
PHST- 2007/02/01 09:00 [pubmed]
PHST- 2007/05/31 09:00 [medline]
PHST- 2007/02/01 09:00 [entrez]
AID - fj.06-6661com [pii]
AID - 10.1096/fj.06-6661com [doi]
PST - ppublish
SO  - FASEB J. 2007 May;21(7):1422-32. doi: 10.1096/fj.06-6661com. Epub 2007 Jan 30.