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Laser Induced Myocardial Angiogenesis

激光诱导心肌血管生成

基本信息

批准号：
6749558
负责人：
Keith A Horvath
金额：
$ 16.34万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-15 至 2005-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6749558
关键词：
angiogenesis disease /disorder model echocardiography electromagnetic radiation fibroblast growth factor heart revascularization immunocytochemistry lasers magnetic resonance imaging messenger RNA microcapsule myocardial ischemia /hypoxia myocardium reperfusion swine tissue /cell culture transfection /expression vector vascular endothelial growth factors

项目摘要

DESCRIPTION (Provided by Applicant): There are an increasing number of patients with disabling angina as a result ot end-stage coronary artery disease. Transmyocardial laser revascularization (TMR) was developed to provide an option for these patients. who are not amenable to conventional methods of revascularization. Clinically, TMR successfully reduces anginal symptoms and improves the quality of the patient's life. The exact mechanism whereby TMR achieves these results is unclear. The objective of this study is to investigate the importance of angiogenesis as a mechanism of TMR. Specifically to determine if there is an upregulation of angiogenic growth factors after TMR. With more endogenous production of angiogens, new blood vessels should develop, perfusion increase and function improve. The potential synergistic response to the addition of exogenous angiogenic growth factors in combination with TMR will be examined. Variations in the response due to different wavelengths of laser light and differences in tissue penetration of this light will be studied. An established animal model of chronic myocardial ischemia will be employed. The angiogenic response will be assessed: 1.) on a molecular basis by demonstrating an increase in the mRNA for bFGF and VEGF; 2.) histologically by an increase in new blood vessels. Perfusion changes will be assessed by colored microspheres and perfusion MRI. Functional changes will be monitored by stress echocardiography and cine MRI. Further enhancement of the angiogenic response will be achieved by the intramyocardial addition of bFGF protein and by VEGF delivered via an adenoviral mediated gene transfer. Finally the differences in TMR by infrared light (carbon dioxide) versus ultraviolet light (excimer) will be assessed. While the clinical results are encouraging, better understanding of the mechanisms of TMR will lead to better treatment for these patients.

描述（由申请人提供）：患者数量不断增加由于终末期冠状动脉疾病导致的心绞痛。激光血运重建术（TMR）的开发是为了提供一种这些患者的选择。他们不适合传统的方法，血运重建临床上，TMR成功地减少了心绞痛症状，提高病人的生活质量。TMR的确切机制实现这些结果是不清楚的。本研究的目的是研究血管生成作为TMR机制的重要性。具体以确定是否有血管生成生长因子的上调后， TMR。随着更多的内源性血管生成素的产生，发育、灌注增加和功能改善。潜在的协同效应对加入外源性血管生成生长因子组合的反应将对TMR进行检查。由于不同的原因，激光的波长和该光的组织穿透的差异将被研究。慢性心肌缺血动物模型的建立将被雇用。将评估血管生成反应：1.）在分子通过证明bFGF和VEGF的mRNA增加来确定基础; 2.）在组织学上是由于新血管的增加。灌注变化将是通过彩色微球和灌注MRI评估。功能变化将是通过负荷超声心动图和磁共振成像监测。进一步加强通过心肌内加入bFGF将实现血管生成反应蛋白和通过腺病毒介导的基因转移递送的VEGF。最后红外光（二氧化碳）与紫外光在TMR中的差异光（受激准分子）将被评估。虽然临床结果令人鼓舞，更好地理解TMR的机制将有助于更好地治疗这些病人。