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The Preliminary Research On Therapeutic Angiogenesis Induced By Angiogenic Factor Directed By The Targeted Delivery System Of Ultrasound Mediated Cavitation Of Microbubbles

Posted on:2003-11-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z J ZhouFull Text:PDF
GTID:1104360092465554Subject:Internal Medicine : Cardiovascular Disease
Abstract/Summary:PDF Full Text Request
Introduction 1. BackgroundCoronary Heart Disease (CHD),which essence is ischmia and hxpoxia,is publicly recognized as main threat for human health and cause the leading death worldwide. With the guidance of evidence medicine,much achievement have been made on the treatment of CAD,especially acute myocardial infarction over the past decades due to lots of newly-found drugs and the reperfusion therapies represented by coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA);however,a lot of issues remain resolved. A growing number of patients neither are suitable for candidates for conventional intervention therapies secondary to anatomical constraints imposed by the severity or extent of their coronary artery disease and some systematical condition such as diabetes and tumor,nor can they get enough blood supply under intervention. If such condition developed,the ischemic myocardium would be doomed to apoptosis,necrosis and fibrosis. It's urgent for people to seek other biological revascularization strategy,and a large body of work involved in both therapeutic angiogensis and stem cell graft are hopefully under way.Normally microcirculation compensation of ischemic heart includes microvessel enlargement,angiogensis and collateral vessel development between artery and vein. However,even nitrates and calcium antagonist were fully administrated,intrinsic microcirculation adjustment still could not reach beyond the basic demand of oxygen and blood of ischemic myocardium,therefore therapeutic angiogenesis induced by exogenesis growth factor which can initiate the formation of a plexus of collateral vessels in zones of ischemic myocardium serve to relieve angina and to improve advanced myocardial ischemia at the base of drug therapy and revascularization intervention. Angiogenesis,which is called "molecular graft of vessels",is a complex and cascade process that involves in stimulation of endothelial cell proliferation and migration by a huge amount of antagonist and agonistgrowth factors,including the fibroblast growth factor (FGF) family,vascular endothelial growth factor (VEGF) family,angiopoietin,ephrins and thrombospondin-1 through stimulating high affinity receptors and signal transduction passway of endothelial cells,and those mitogen factors and cascades seems to act in a coordinated way to achieve this process. The vascular endothelial growth factor(VEGF) was identified as endothelial cell specific mitogen. It has been shown to be involved in endothelial cell proliferation and blood vessel formation. VEGF mediates its function through its specific receptor on the vascular endothelial cell surface. VEGF plays important roles in variety of physiological and pathological processes including embryogenesis,tumor and some cardiovascular diseases. The rapid development of molecular biology in myocardiovascular scope and growth factor therapy offers to clinical practices. Although several clinical trials involved various endovascular delivery devices have been designed for angiogenesis,such as bolus injection of naked plasmid DNA encoding phVEGF165,phVEGF121 and bFGF of recombinated virus,either in pericardium,direct myocardium at the time of thoracotomy or intracoronary injection and endoluminal delivering,the limitations of such delivery including the possibility of increased vascular trauma,high risk,low efficiency of localization,inconsistency of delivery,and rapid washout of the agents from the vascular wall after delivery prevent the progres of further development of angiogenesis.Ultrasound,which has been playing a very important role in targeted delivering of gene and active agents,merits further exploration. The aim is to use ultrasound and ultrasound echo contrast agents to offer a targeting delivering procedure,called the delivery system of ultrasound-mediated destruction and cavitation of targeted microbubbles. The core of the approach,which depend on the cavitation effect of microbubble under ultrasound field,is locally delivered pharmacological drugs or t...
Keywords/Search Tags:Delivery systerm of ultrasound-mediated destruction and cavitation of targeted microbubbles, Report gene, Gene recombination, Gene expression, Transfection, Vascular endothelium growth factor, Isoform, Angiogenesis
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