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Effects Of Nuclear Factor κB And Cyclooxygenase-2 On Coronary Artery Disease And Restenosis

Posted on:2004-03-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:X Q HuFull Text:PDF
GTID:1104360092487073Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background: Restenosis is the most important complication which limits the long-term success after percutanous coronary intervetion (PCI). Increasing evidences reveal that inflammation plays a pivotal role in the initiation and progression of restenosis. Nuclear Factor K B (NF- κ B) is a transcription factor, which involves in inflammation and growth response. When NF- K B is activated, it upregulates COX-2 gene expression. COX-2 is an inducible isoform of COX. COX-2 is the key enzyme that regulates the amount and duration of prostaglandin (PG). PG plays an important role in inflammation.Besides its hypolipidemic properties, statins have other anti-atherosclerosis mechanisms. Such as improving endothelial function, inhibiting proliferation of smooth muscle cells and reducing inflammatory response, etc. It has been demonstrated that statins can inhibit vessel intimal hyperplasia after balloon injury, but clinical data about statin on restenosis after balloon angioplasty are conflicting. The mechanism is still under investigation. NF- κB plays a crucial role in the regulation of inflammation. NF- κ B is present on all atherom- derived cells and can induce the cells to produce proimflammatory cytokines, COX-2,cell adhesion molecules and inflammatory mediators. COX-2 may regulate intimal hyprplasia. The anti-intimal hyperplasia effect of statins may be linked to COX-2 inhibition.C-reactive protein is a kind of inflammatory markers. High-sensitivety C-reactive protein (hsCRP) may provide a novel method for detecting individuals at high risk of plaque rupture. Several large-scale prospective studies demonstrate that hsCRP is a strong independent. predictor of future myocardial infarction among apparently healthy men and women. The relatioship between COX-2 and. restenosis is unknown.Part One: Relationship between Intimal Hyperplasia and NF- κ B, COX-2 Expression in Hypercholesterolemic rabbits carotid artery after balloon injuryObjectives: To investigate the change of NF- κ B and COX-2 in hypercholesterolemic rabbits carotid artery injured by balloon and their relationship with intimal hyperplasia. To explore the potential mechanism of restenosis.Methods: Twenty-five New Zealand male rabbits were studied. They were fed with atherogenic diet. Four weeks later, balloon injury was conducted in right carotid artery respectively. A few rabbits were killed at 6h, 24h, 1W, 2W and 4W. Blood samples and right carotid artery were collected. Intime hyperplasia was studied by histological morphology method. The expression of NF-κ B was measured by in-situ hypridization (ISH). The expression of-tissue COX-2 mRNA was determined by reverse transcription polymerase chain reaction(RT-PCR).Result:1. Intimal hyperplasia was present at day 7 after balboon injury, became more obvious at day 14 and in progression at day 28. The media area was not changed .The intima/media ratio increased as time went on. No change was observed in control group.2. NF-κ B mRNA expression was trace in the carotid atery of the hypercholesterolemic rabbits without balloon injury. The expression increased significantly after balloon injury,3. COX-2 mRNA expression was trace in the carotid atery of the hypercholesterolemic rabbits without balloon injury. The expression increased significantly after balloon injury.4. After balloon injury , NF-κB ,COX-2 expressed stronger in injury group than in control group.Conclusions:1. NF-κB ,COX-2 mRNA expression was trace in the carotid atery of the hypercholesterolemic rabbits without balloon injury, which indicated that NF-κB ,COX-2may play an important role in the early stage of athrosclerosis.2. NF-κB may be the promtor factor of inflammatory response after ballooninjury.3. NF-κB ,COX-2 expressed stronger in injury group than in control group, which indicated that NF-KB ,COX-2 may play an important role in restenosis caused by balloon injury.4. Hypercholesterolemic rabbits carotid a...
Keywords/Search Tags:Cyclooxygenase-2
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