PMID- 22227562
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20211109
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 46
IP  - 5
DP  - 2012 May
TI  - Increased hyperoxia-induced lung injury in nitric oxide synthase 2 null mice is 
      mediated via angiopoietin 2.
PG  - 668-76
LID - 10.1165/rcmb.2011-0074OC [doi]
AB  - Supplemental oxygen is frequently prescribed. However, prolonged exposure to high 
      concentrations of oxygen causes hyperoxic acute lung injury (HALI), which 
      manifests as acute respiratory distress syndrome in adults and leads to 
      bronchopulmonary dysplasia in newborns (NBs). Nitric oxide (NO), NO synthases 
      (NOSs), and angiopoietin (Ang) 2 have been implicated in the pathogenesis of 
      HALI. However, the mechanisms of the contributions of NOS/NO and the 
      relationship(s) between NOS/NO and Ang2 have not been addressed. In addition, the 
      relevance of these moieties in adults and NBs has not been evaluated. To address 
      these issues, we compared the responses in hyperoxia of wild-type (NOS [+/+]) and 
      NOS null (-/-) young adult and NB mice. When compared with NOS2(+/+) adult 
      controls, NOS2(-/-) animals manifest exaggerated alveolar-capillary protein leak 
      and premature death. These responses were associated with enhanced levels of 
      structural cell death, enhanced expression of proapoptotic regulatory proteins, 
      and Ang2. Importantly, silencing RNA knockdown of Ang2 decreased the levels of 
      cell death and the expression of proapoptotic mediators. These effects were at 
      least partially NOS2 specific, and were development dependent, because survival 
      was similar in adult NOS3(+/+) and NOS3(-/-) mice and NB NOS2(+/+) and NOS2(-/-) 
      mice, respectively. These studies demonstrate that NOS2 plays an important 
      protective role in HALI in adult animals. They also demonstrate that this 
      response is mediated, at least in part, by the ability of NOS2 to inhibit 
      hyperoxia-induced Ang2 production and thereby decrease Ang2-induced tissue 
      injury.
FAU - Bhandari, Vineet
AU  - Bhandari V
AD  - Division of Perinatal Medicine, Yale University School of Medicine, Department of 
      Pediatrics, Children's Hospital, 20 York Street, New Haven, CT 06520-8057, USA. 
      vineet.bhandari@yale.edu
FAU - Choo-Wing, Rayman
AU  - Choo-Wing R
FAU - Harijith, Anantha
AU  - Harijith A
FAU - Sun, Huanxing
AU  - Sun H
FAU - Syed, Mansoor Ali
AU  - Syed MA
FAU - Homer, Robert J
AU  - Homer RJ
FAU - Elias, Jack A
AU  - Elias JA
LA  - eng
GR  - HL-64642/HL/NHLBI NIH HHS/United States
GR  - K08 HL074195/HL/NHLBI NIH HHS/United States
GR  - HL-61904/HL/NHLBI NIH HHS/United States
GR  - P01 HL056389/HL/NHLBI NIH HHS/United States
GR  - HL-85103/HL/NHLBI NIH HHS/United States
GR  - HL-56389/HL/NHLBI NIH HHS/United States
GR  - HL-74195/HL/NHLBI NIH HHS/United States
GR  - R01 HL085103/HL/NHLBI NIH HHS/United States
GR  - P50 HL056389/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 - 20120106
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Angiopoietin-2)
RN  - 0 (RNA, Small Interfering)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Angiopoietin-2/*physiology
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid
MH  - Gene Expression Regulation, Enzymologic
MH  - Hyperoxia/*complications
MH  - Lung Injury/enzymology/*etiology
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase Type II/genetics/*metabolism
MH  - RNA, Small Interfering
PMC - PMC3359903
EDAT- 2012/01/10 06:00
MHDA- 2012/06/26 06:00
PMCR- 2013/05/01
CRDT- 2012/01/10 06:00
PHST- 2012/01/10 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - rcmb.2011-0074OC [pii]
AID - 2011-0074OC [pii]
AID - 10.1165/rcmb.2011-0074OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2012 May;46(5):668-76. doi: 10.1165/rcmb.2011-0074OC. 
      Epub 2012 Jan 6.