腺病毒轉載 dimethylarginine dimethylaminohydrolase 載體調節血管內皮細胞及平滑肌的生理功能; Elucidating the effects of adenovirus-mediated DDAH on vascular endothelial and smooth muscle cells function.

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Title:	腺病毒轉載 dimethylarginine dimethylaminohydrolase 載體調節血管內皮細胞及平滑肌的生理功能;Elucidating the effects of adenovirus-mediated DDAH on vascular endothelial and smooth muscle cells function.
Authors:	張仕杰;Chang, Shih-Chieh
Contributors:	中國醫藥大學醫學研究所
Keywords:	一氧化氮;血管內皮細胞;血管平滑肌細胞;nitric oxide;vescular endothelium cell;vescular smooth muscle cell
Date:	2004
Issue Date:	2010-01-20 16:53:55 (UTC+8)
Abstract:	在本篇研究中，藉由探討細胞增生（proliferation）、細胞轉移（cell migration）等機制，評估腺病毒轉載DDAH載體對於血管內皮細胞及平滑肌所扮演的調控的角色。在接受氣球擴張手術治療的病人當中，有百分之三十到五十的病人會有再阻塞的情形發生，這對預後造成一項很大的阻礙，愈來愈多的證據指出一氧化氮由於可減少收縮力，所以在心血管生理中扮演一個主要的調控角色，同時，一個內生性一氧化氮合成?的抑制劑ADMA也被發現會抑制一氧化氮合成?的活性，導致NO的生合成受到影響，幸而血管中有一個酵素DDAH得以專一性來代謝ADMA的內生性酵素。為了研究ADMA－DDAH路徑是否也能調控再阻塞的機轉，我們使用了腺病毒載體在細胞及動物模式過度表現DDAH的方法下，評估於內皮細胞及平滑肌細胞的影響，並藉由動物實驗探究使用於臨床治療上的潛力。; Restenosis is a major clinical problem that occurs in 30% to 50% of patients who undergo a Percutaneous Transluminal Coronary Angioplasty (PTCA) procedure and limits its long-term success. Accumulating evidence has indicated that Nitric Oxide (NO) is a major regulator of cardiovascular physiology and can reduce vascular and cardiac contractility. It is found that an endogenous inhibitors, asymmetric dimethylarginine (ADMA), may regulate NOS activity. A vascular endogenous enzyme, dimethylarginine dimethylaminohydrolase (DDAH), has been found to be the major mediator to metabolize ADMA in vivo. In order to test if the ADMA-DDAH pathway plays a role in restenosis, we used adenovirus as a vector to overexpress DDAH gene in cell and animal models. In the present study, we aim to elucidate the effect of adenovirus-mediated DDAH overexpression in endothelial, smooth muscle cells, and rat vessel to determine its potential therapeutic indication on balloom injury-mediated neointima formation. The translational regulation of DDAH on VCAM-1 was also thoroughly investigated in this thesis.
Appears in Collections:	[Graduate Institute of Medical Science] Theses & dissertations

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