Linked Life Data

16339488

Source:http://linkedlifedata.com/resource/pubmed/id/16339488

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-6
pubmed:abstractText
Autologous saphenous vein bypass grafts (SVG) are frequently compromised by neointimal thickening and subsequent atherosclerosis eventually leading to graft failure. Hyaluronic acid (HA) generated by smooth muscle cells (SMC) is thought to augment the progression of atherosclerosis. The aim of the present study was (1) to investigate HA accumulation in native and explanted arterialized SVG, (2) to identify factors that regulate HA synthase (HAS) expression and HA synthesis, and (3) to study the function of the HAS2 isoform. In native SVG, expression of all 3 HAS isoforms was detected by RT-PCR. Histochemistry revealed that native and arterialized human saphenous vein segments were characterized by marked deposition of HA in association with SMC. Interestingly, in contrast to native SVG, cyclooxygenase (COX)-2 expression by SMC and macrophages was detected only in arterialized SVG. In vitro in human venous SMC HAS isoforms were found to be differentially regulated. HAS2, HAS1, and HA synthesis were strongly induced by vasodilatory prostaglandins via Gs-coupled prostaglandin receptors. In addition, thrombin induced HAS2 via activation of PAR1 and interleukin 1beta was the only factor that induced HAS3. By small interfering RNA against HAS2, it was shown that HAS2 mediated HA synthesis is critically involved in cell cycle progression through G1/S phase and SMC proliferation. In conclusion, the present study shows that HA-rich extracellular matrix is maintained after arterialization of vein grafts and might contribute to graft failure because of its proproliferative function in venous SMC. Furthermore, COX-2-dependent prostaglandins may play a key role in the regulation of HA synthesis in arterialized vein grafts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16339488-Adult, pubmed-meshheading:16339488-Aged, pubmed-meshheading:16339488-Aged, 80 and over, pubmed-meshheading:16339488-Cells, Cultured, pubmed-meshheading:16339488-Cyclooxygenase 2, pubmed-meshheading:16339488-Female, pubmed-meshheading:16339488-Gene Expression Regulation, Enzymologic, pubmed-meshheading:16339488-Glucuronosyltransferase, pubmed-meshheading:16339488-Graft Occlusion, Vascular, pubmed-meshheading:16339488-Humans, pubmed-meshheading:16339488-Hyaluronic Acid, pubmed-meshheading:16339488-Interleukin-1, pubmed-meshheading:16339488-Isoenzymes, pubmed-meshheading:16339488-Male, pubmed-meshheading:16339488-Middle Aged, pubmed-meshheading:16339488-Muscle, Smooth, Vascular, pubmed-meshheading:16339488-Platelet-Derived Growth Factor, pubmed-meshheading:16339488-RNA, Small Interfering, pubmed-meshheading:16339488-Saphenous Vein, pubmed-meshheading:16339488-Thrombin, pubmed-meshheading:16339488-Tunica Intima
pubmed:year
2006
pubmed:articleTitle
Differential regulation of hyaluronic acid synthase isoforms in human saphenous vein smooth muscle cells: possible implications for vein graft stenosis.
pubmed:affiliation
Molekulare Pharmakologie, Heinrich Heine Universität, Düsseldorf, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't