Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-5-6
pubmed:abstractText
cGMP-specific phosphodiesterase 5 (PDE5) inhibition has been shown to be effective in improving pulmonary haemodynamics in both animal models and clinic patients with pulmonary hypertension. Here, we reveal a novel mechanism whereby PDE5 inhibition suppresses serotonin signalling and consequent cellular proliferation in primary cultured pulmonary artery smooth muscle cells (PASMCs). 1 microM serotonin induced 4.15-fold increases in DNA synthesis compared with control; this was accompanied by significant Ras homolog gene family member A (RhoA) activation and ERK1/2 MAP kinase phosphorylation/nucleus translocation. Furthermore, inhibition of Rho-associated kinase (ROCK) abolished serotonin-triggered DNA synthesis and ERK1/2 nucleus translocation without changing ERK1/2 phosphorylation, indicating that ERK1/2 phosphorylation and nucleus translocation are coupled to different upstream effectors. Pre-exposure of cells to sildenafil dose-dependently blocked the activation of these signalling pathways and elevated DNA synthesis. The inhibitive effects of sildenafil, however, were fully reversed by concomitant presence of PKG inhibitor in cells. These data suggest that RhoA and ERK1/2 pathways are partially cross-talked and concordantly mediate serotonin-stimulated PASMCs proliferation thereby vascular remodelling leading to the occurrence of pulmonary hypertension. Meanwhile, these two pathways are also separately modulated by enhanced cGMP-PKG signalling derived from inhibition of PDE5 with sildenafil to confer the overall roles of sildenafil against pulmonary hypertension.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP-Dependent Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase 5 Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Piperazines, http://linkedlifedata.com/resource/pubmed/chemical/Purines, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin, http://linkedlifedata.com/resource/pubmed/chemical/Sulfones, http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases, http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein, http://linkedlifedata.com/resource/pubmed/chemical/sildenafil
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1096-1186
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
312-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19416631-Animals, pubmed-meshheading:19416631-Cell Proliferation, pubmed-meshheading:19416631-Cells, Cultured, pubmed-meshheading:19416631-Cyclic GMP-Dependent Protein Kinases, pubmed-meshheading:19416631-DNA, pubmed-meshheading:19416631-Enzyme Activation, pubmed-meshheading:19416631-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:19416631-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:19416631-Muscle, Smooth, Vascular, pubmed-meshheading:19416631-Myocytes, Smooth Muscle, pubmed-meshheading:19416631-Phosphodiesterase 5 Inhibitors, pubmed-meshheading:19416631-Phosphorylation, pubmed-meshheading:19416631-Piperazines, pubmed-meshheading:19416631-Pulmonary Artery, pubmed-meshheading:19416631-Purines, pubmed-meshheading:19416631-Rats, pubmed-meshheading:19416631-Rats, Sprague-Dawley, pubmed-meshheading:19416631-Serotonin, pubmed-meshheading:19416631-Signal Transduction, pubmed-meshheading:19416631-Sulfones, pubmed-meshheading:19416631-rho-Associated Kinases, pubmed-meshheading:19416631-rhoA GTP-Binding Protein
pubmed:year
2009
pubmed:articleTitle
Inhibition of cGMP phosphodiesterase 5 suppresses serotonin signalling in pulmonary artery smooth muscles cells.
pubmed:affiliation
Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, No. 157, West 5th Road, Xi'an, Shaanxi 710004, PR China. manxiangli@hotmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't