PMID- 17322376
OWN - NLM
STAT- MEDLINE
DCOM- 20070501
LR  - 20240414
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 170
IP  - 3
DP  - 2007 Mar
TI  - Glyceryl trinitrate inhibits hypoxia/reoxygenation-induced apoptosis in the 
      syncytiotrophoblast of the human placenta: therapeutic implications for 
      preeclampsia.
PG  - 909-20
AB  - Damage of the placenta resulting from ischemia-reperfusion is important to the 
      pathophysiology of preeclampsia. Here we investigated whether low concentrations 
      of glyceryl trinitrate (GTN), a nitric oxide mimetic with anti-apoptotic 
      properties, inhibit hypoxia/reoxygenation-induced apoptosis in the 
      syncytiotrophoblast of chorionic villous explants from human placentas. Compared 
      with villi analyzed immediately after delivery or maintained under normoxic 
      conditions, villi exposed to a 6-hour cycle of hypoxia/reoxygenation exhibited 
      greater numbers of syncytiotrophoblasts with terminal dUTP nick-end labeling 
      (TUNEL)-positive nuclei in the syncytiotrophoblast. This increased number of 
      TUNEL-positive nuclei was paralleled by higher levels of 4-hydroxynonenal (marker 
      of lipid peroxidation), nitrotyrosine residues, and active caspase-3 and 
      polyADP-ribose polymerase expression. Morphological analysis of explants exposed 
      to hypoxia/reoxygenation revealed apoptotic and aponecrotic features similar to 
      those of chorionic villi from preeclamptic pregnancies. Treatment with GTN during 
      the hy-poxia/reoxygenation cycle blocked the increases in the number of 
      TUNEL-positive nuclei and in the levels of 4-hydroxynonenal, nitrotyrosine, and 
      active caspase-3. Incubation with GTN also attenuated the 
      hypoxia/reoxygenation-induced polyADP-ribose polymerase expression and the 
      apoptotic and aponecrotic morphological alterations. These results suggest that 
      small concentrations of nitric oxide protect chorionic villi from 
      hypoxia/reoxygenation-induced damage and provide a rationale for the use of low 
      doses of nitric oxide mimetics in the treatment and/or prevention of 
      preeclampsia.
FAU - Belkacemi, Louiza
AU  - Belkacemi L
AD  - Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, 
      Canada.
FAU - Bainbridge, Shannon A
AU  - Bainbridge SA
FAU - Dickinson, Michelle A
AU  - Dickinson MA
FAU - Smith, Graeme N
AU  - Smith GN
FAU - Graham, Charles H
AU  - Graham CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Aldehydes)
RN  - 0 (COL11A2 protein, human)
RN  - 0 (Collagen Type XI)
RN  - 0 (Tocolytic Agents)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 3.4.22.- (Caspase 3)
RN  - G59M7S0WS3 (Nitroglycerin)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Aldehydes/metabolism
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Caspase 3/drug effects
MH  - Collagen Type XI/drug effects
MH  - Female
MH  - Humans
MH  - Hypoxia/physiopathology
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Microscopy, Electron, Transmission
MH  - Nitroglycerin/*pharmacology
MH  - Organ Culture Techniques
MH  - Pre-Eclampsia/*drug therapy
MH  - Pregnancy
MH  - Reperfusion Injury/*prevention & control
MH  - Tocolytic Agents/*pharmacology
MH  - Trophoblasts/*drug effects/pathology
MH  - Tyrosine/analogs & derivatives/drug effects
PMC - PMC1864864
EDAT- 2007/02/27 09:00
MHDA- 2007/05/02 09:00
PMCR- 2007/09/01
CRDT- 2007/02/27 09:00
PHST- 2007/02/27 09:00 [pubmed]
PHST- 2007/05/02 09:00 [medline]
PHST- 2007/02/27 09:00 [entrez]
PHST- 2007/09/01 00:00 [pmc-release]
AID - S0002-9440(10)60912-1 [pii]
AID - 10.2353/ajpath.2007.060665 [doi]
PST - ppublish
SO  - Am J Pathol. 2007 Mar;170(3):909-20. doi: 10.2353/ajpath.2007.060665.