RGD Reference Report - Molecular mechanisms regulating the vascular prostacyclin pathways and their adaptation during pregnancy and in the newborn. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Molecular mechanisms regulating the vascular prostacyclin pathways and their adaptation during pregnancy and in the newborn.

Authors: Majed, BH  Khalil, RA 
Citation: Majed BH and Khalil RA, Pharmacol Rev. 2012 Jul;64(3):540-82. doi: 10.1124/pr.111.004770. Epub 2012 Jun 7.
RGD ID: 8552712
Pubmed: PMID:22679221   (View Abstract at PubMed)
PMCID: PMC3400831   (View Article at PubMed Central)
DOI: DOI:10.1124/pr.111.004770   (Journal Full-text)

Prostacyclin (PGI(2)) is a member of the prostanoid group of eicosanoids that regulate homeostasis, hemostasis, smooth muscle function and inflammation. Prostanoids are derived from arachidonic acid by the sequential actions of phospholipase A(2), cyclooxygenase (COX), and specific prostaglandin (PG) synthases. There are two major COX enzymes, COX1 and COX2, that differ in structure, tissue distribution, subcellular localization, and function. COX1 is largely constitutively expressed, whereas COX2 is induced at sites of inflammation and vascular injury. PGI(2) is produced by endothelial cells and influences many cardiovascular processes. PGI(2) acts mainly on the prostacyclin (IP) receptor, but because of receptor homology, PGI(2) analogs such as iloprost may act on other prostanoid receptors with variable affinities. PGI(2)/IP interaction stimulates G protein-coupled increase in cAMP and protein kinase A, resulting in decreased [Ca(2+)](i), and could also cause inhibition of Rho kinase, leading to vascular smooth muscle relaxation. In addition, PGI(2) intracrine signaling may target nuclear peroxisome proliferator-activated receptors and regulate gene transcription. PGI(2) counteracts the vasoconstrictor and platelet aggregation effects of thromboxane A(2) (TXA(2)), and both prostanoids create an important balance in cardiovascular homeostasis. The PGI(2)/TXA(2) balance is particularly critical in the regulation of maternal and fetal vascular function during pregnancy and in the newborn. A decrease in PGI(2)/TXA(2) ratio in the maternal, fetal, and neonatal circulation may contribute to preeclampsia, intrauterine growth restriction, and persistent pulmonary hypertension of the newborn (PPHN), respectively. On the other hand, increased PGI(2) activity may contribute to patent ductus arteriosus (PDA) and intraventricular hemorrhage in premature newborns. These observations have raised interest in the use of COX inhibitors and PGI(2) analogs in the management of pregnancy-associated and neonatal vascular disorders. The use of aspirin to decrease TXA(2) synthesis has shown little benefit in preeclampsia, whereas indomethacin and ibuprofen are used effectively to close PDA in the premature newborn. PGI(2) analogs have been used effectively in primary pulmonary hypertension in adults and have shown promise in PPHN. Careful examination of PGI(2) metabolism and the complex interplay with other prostanoids will help design specific modulators of the PGI(2)-dependent pathways for the management of pregnancy-related and neonatal vascular disorders.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PLA2G4AHumancyclooxygenase mediated pathway of arachidonic acid metabolism   TAS  RGD 
PTGS1Humancyclooxygenase mediated pathway of arachidonic acid metabolism   TAS  RGD 
PTGS2Humancyclooxygenase mediated pathway of arachidonic acid metabolism   TAS  RGD 
Pla2g4aMousecyclooxygenase mediated pathway of arachidonic acid metabolism   ISOPLA2G4A (Homo sapiens) RGD 
Pla2g4aRatcyclooxygenase mediated pathway of arachidonic acid metabolism   ISOPLA2G4A (Homo sapiens) RGD 
Ptgs1Ratcyclooxygenase mediated pathway of arachidonic acid metabolism   ISOPTGS1 (Homo sapiens) RGD 
Ptgs1Mousecyclooxygenase mediated pathway of arachidonic acid metabolism   ISOPTGS1 (Homo sapiens) RGD 
Ptgs2Ratcyclooxygenase mediated pathway of arachidonic acid metabolism   ISOPTGS2 (Homo sapiens) RGD 
Ptgs2Mousecyclooxygenase mediated pathway of arachidonic acid metabolism   ISOPTGS2 (Homo sapiens) RGD 
PTGISHumanprostacyclin biosynthetic pathway  TAS  RGD 
PtgisRatprostacyclin biosynthetic pathway  ISOPTGIS (Homo sapiens) RGD 
PtgisMouseprostacyclin biosynthetic pathway  ISOPTGIS (Homo sapiens) RGD 
HPGDSHumanprostaglandin biosynthetic pathway  TAS  RGD 
HpgdsRatprostaglandin biosynthetic pathway  ISOHPGDS (Homo sapiens) RGD 
HpgdsMouseprostaglandin biosynthetic pathway  ISOHPGDS (Homo sapiens) RGD 
PTGDSHumanprostaglandin biosynthetic pathway  TAS  RGD 
PTGESHumanprostaglandin biosynthetic pathway  TAS  RGD 
PTGES2Humanprostaglandin biosynthetic pathway  TAS  RGD 
PTGES3Humanprostaglandin biosynthetic pathway  TAS  RGD 
PtgdsRatprostaglandin biosynthetic pathway  ISOPTGDS (Homo sapiens) RGD 
PtgdsMouseprostaglandin biosynthetic pathway  ISOPTGDS (Homo sapiens) RGD 
PtgesRatprostaglandin biosynthetic pathway  ISOPTGES (Homo sapiens) RGD 
PtgesMouseprostaglandin biosynthetic pathway  ISOPTGES (Homo sapiens) RGD 
Ptges2Ratprostaglandin biosynthetic pathway  ISOPTGES2 (Homo sapiens) RGD 
Ptges2Mouseprostaglandin biosynthetic pathway  ISOPTGES2 (Homo sapiens) RGD 
Ptges3Ratprostaglandin biosynthetic pathway  ISOPTGES3 (Homo sapiens) RGD 
Ptges3Mouseprostaglandin biosynthetic pathway  ISOPTGES3 (Homo sapiens) RGD 
PTGS1Humanprostanoid biosynthetic pathway   TAS  RGD 
PTGS2Humanprostanoid biosynthetic pathway   TAS  RGD 
Ptgs1Mouseprostanoid biosynthetic pathway   ISOPTGS1 (Homo sapiens) RGD 
Ptgs1Ratprostanoid biosynthetic pathway   ISOPTGS1 (Homo sapiens) RGD 
Ptgs2Mouseprostanoid biosynthetic pathway   ISOPTGS2 (Homo sapiens) RGD 
Ptgs2Ratprostanoid biosynthetic pathway   ISOPTGS2 (Homo sapiens) RGD 
TBXAS1Humanthromboxane biosynthetic pathway  TAS  RGD 
Tbxas1Ratthromboxane biosynthetic pathway  ISOTBXAS1 (Homo sapiens) RGD 
Tbxas1Mousethromboxane biosynthetic pathway  ISOTBXAS1 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Hpgds  (hematopoietic prostaglandin D synthase)
Pla2g4a  (phospholipase A2 group 4A)
Ptgds  (prostaglandin D2 synthase)
Ptges  (prostaglandin E synthase)
Ptges2  (prostaglandin E synthase 2)
Ptges3  (prostaglandin E synthase 3)
Ptgis  (prostaglandin I2 synthase)
Ptgs1  (prostaglandin-endoperoxide synthase 1)
Ptgs2  (prostaglandin-endoperoxide synthase 2)
Tbxas1  (thromboxane A synthase 1)

Genes (Mus musculus)
Hpgds  (hematopoietic prostaglandin D synthase)
Pla2g4a  (phospholipase A2, group IVA (cytosolic, calcium-dependent))
Ptgds  (prostaglandin D2 synthase (brain))
Ptges  (prostaglandin E synthase)
Ptges2  (prostaglandin E synthase 2)
Ptges3  (prostaglandin E synthase 3)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)
Ptgs1  (prostaglandin-endoperoxide synthase 1)
Ptgs2  (prostaglandin-endoperoxide synthase 2)
Tbxas1  (thromboxane A synthase 1, platelet)

Genes (Homo sapiens)
HPGDS  (hematopoietic prostaglandin D synthase)
PLA2G4A  (phospholipase A2 group IVA)
PTGDS  (prostaglandin D2 synthase)
PTGES  (prostaglandin E synthase)
PTGES2  (prostaglandin E synthase 2)
PTGES3  (prostaglandin E synthase 3)
PTGIS  (prostaglandin I2 synthase)
PTGS1  (prostaglandin-endoperoxide synthase 1)
PTGS2  (prostaglandin-endoperoxide synthase 2)
TBXAS1  (thromboxane A synthase 1)


Additional Information