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The Value of Pregnancy Associated Plasma Protein A and IVS6+95Gene Polymorphism in Prediction of Restenosis after Percutaneous Coronary Intervention

Author: ZhangTeng
Tutor: CuiLianQun
School: Shandong University
Course: Internal Medicine
Keywords: High sensitivity C-reactive protein Pregnancy associated plasma proteinA Gene polymorphism Percutaneous coronary intervention Coronary restenosis
CLC: R654.2
Type: Master's thesis
Year: 2013
Downloads: 12
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Abstract


Background:Coronary atherosclerotic heart disease is one of diseases with the highest morbidity and mortality rates. CAD is a chronic inflammatory reaction involved with genetic and environmental factors. On the basis of the blocked coronary artery and stimulation of inflammatory factors, the rupture of vulnerable plaque, induced vasospasm, platelet adhesion and aggregation and not completely blocked thrombosis are likely to happen, so that blood flow decreases dramatically, leading to myocardial ischemia, hypoxia and clinical manifestations of unstable angina. In recent years, with the emergence of drug-eluting stents, indication of percutaneous coronary intervention becomes broader, and becomes an important means of intervention which can relieve symptoms and improve quality of life. However, there are still about10%of patients facing restenosis after PCI and conventional double antiplatelet therapy, thus affecting the surgical effects and long-term prognosis. How to accurately predict and identify patients with restenosis postoperative and give an effective interventions has become an urgent problem to solve.At present, the main accurate and effective means of evaluating restenosis in clinic are coronary angiography (the coronary angiography CAG) and intravascular ultrasound (intravascular ultrasound, IVUS), both of which are not only costly but also invasive. However, non-invasive inflammatory biological markers can be used in risk stratification and disease monitoring of ACS, and have a high clinical value. So to find a new non-invasive and serological inflammatory markers is essential. Pregnancy associated plasma protein A (PAPP-A) is a biological indicator, located on chromosome9. Its molecular weight is800000, composed of two pro-forms of eosinphi major basic protein proMBP with molecular weight of38000and two subunits with molecular weight of200000to500000. It is a member of the zinc ions dependency matrix metalloproteinases matrix metalloproteinase family, and plays a biological role in the insulin-like growth factor axis. PAPP-A is the insulin-like growth factor binding protein-4-specific proteolytic enzyme, which cannot bind insulin-like growth factor after dissociating into two small fragments, so that the free IGF serological concentration becomes high and can promote the proliferation and migration of smooth muscle cell and neointima formation. Thus the chemotaxis of inflammatory cell increases, cytokines release and foam cells increase, derived from macrophages and smooth muscle cells after phagocytosing lipid, while the extracellular matrix degradation accelerats and the fibrous cap-like structure becomes thin, and ultimately plaques rupture.Study found that14exon of PAPP-A exists gene polymorphism and relates to the susceptibility of premature coronary heart disease. Park S also proposed IVS6+95(C/G) gene of PAPP-A existed single nucleotide polymorphism, however its underlying mechanism is still unclear.High sensitivity C reactive protein synthesised and secreted by the liver cells can bind to pneumococcal polysaccharide and is considered as a non-specific inflammatory sensitive marker, when the body is in the inflammatory state, quantities of hs-CRP are released, which can promote macrophage to uptake LDL and ox-LDL, accelerate the intimal injury and increase the expression of EC AM. Finally intimal hyperplasia and restenosis happen.Although in vivo the level of inflammatory cytokines was confirmed to be associated with restenosis after PCI, the relationship betweeen restenosis and PAPP-A and the single nucleotide polymorphisms of its intron IVS6+95((C/G)) is unclear. In this study, we examine the expression levels of PAPP-A, hs-CRP and single nucleotide polymorphism of IVS6+95(C/G) and study the relationship between those markers and restenosis after PCI. The main contents and results of this dissertation are as follows. Objective:To explore the value of pregnancy associated plasma protein A、high sensitivity C-reactive protein and IVS6+95gene polymorphism in prediction of restenosis after percutaneous coronary intervention.Methods:The patients with unstable angina pectoris were performed PCI. Those patients were classified as group A (86cases with related coronary artery lumen loss more than75%in diameter3-9months after PCI) and group B (the rest152cases with related coronary lumen loss less than75%). Serum PAPP-A and hs-CRP levels were examined before and24h after coronary angiography. The gene polymorphisms was analyzed by gene sequencing.Results:Serum PAPP-A and hs-CRP levels were significantly increased In group A and decreased in group B after PCI (P<0.001). The CC gene frequency of PAPP-A gene IVS6+95was significantly higher in group A than in group B(P<0.05). But there were no difference in the frequency of allele C between two groups(P>0.05).Conclusion:PAPP-A and hs-CRP level increase after PCI have a strong power in prediction of coronary artery restenosis after PCI. The polymorphism of PAPP-A gene IVS6+95(C/G) may be associated with postoperative restenosis and CC genotypes may be the foundation of pathogen.

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