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血管内皮生长因子基因作为动脉粥样硬化血栓形成性疾病的遗传标志物以及在冠状动脉疾病基因治疗中的作用。

The role of vascular endothelial growth factor gene as the genetic marker of atherothrombotic disorders and in the gene therapy of coronary artery disease.

作者信息

Petrovic Daniel

机构信息

Institute of Histology and Embryology, Medical Faculty, University of Ljubljana, Korytkova 2, Ljubljana, Slovenia.

出版信息

Cardiovasc Hematol Agents Med Chem. 2010 Jan;8(1):47-54. doi: 10.2174/187152510790796183.

Abstract

Many human diseases are characterized by vasculature disorders. Out of the many players in the angiogenic network, the vascular endothelial growth genes are by far the best characterized. The vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of coronary artery disease (CAD) and in its complication, the acute myocardial infarction (AMI). Several common polymorphisms in the promoter region of the VEGF gene have been reported, but only few single nucleotide polymorphisms (SNPs) have been demonstrated to be associated with variations in VEGF serum concentrations and with a susceptibility to CAD and its complications-acute coronary syndromes. Moreover, the -634 C/G VEGF SNP (rs2010963) has been demonstrated to be associated with AMI and the development of heart failure after AMI. Gene-based therapy for patients with refractory CAD has been the subject of extensive investigation. Preclinical studies have shown promise for the delivery of VEGF gene for treating CAD, whereas the results of randomized placebo-controlled trials have not demonstrated unequivocal evidence of efficacy. To conclude, at present the role of VEGF and VEGF SNPs in pathogenesis of AMI and the development of heart failure after AMI is still uncertain and remains to be determined. Obviously, larger studies as well as functional studies are needed to confirm the role of VEGF SNPs in AMI and its complications after AMI.

摘要

许多人类疾病都以血管系统紊乱为特征。在血管生成网络的众多参与者中,血管内皮生长基因是目前研究最为透彻的。血管内皮生长因子(VEGF)与冠状动脉疾病(CAD)的发病机制及其并发症急性心肌梗死(AMI)有关。VEGF基因启动子区域已报道了几种常见的多态性,但仅有少数单核苷酸多态性(SNP)被证明与VEGF血清浓度变化以及CAD及其并发症急性冠状动脉综合征的易感性相关。此外,-634 C/G VEGF SNP(rs2010963)已被证明与AMI以及AMI后心力衰竭的发生有关。针对难治性CAD患者的基因治疗一直是广泛研究的主题。临床前研究显示了VEGF基因治疗CAD的前景,而随机安慰剂对照试验的结果并未明确证明其疗效。总之,目前VEGF和VEGF SNP在AMI发病机制以及AMI后心力衰竭发生中的作用仍不确定,有待进一步确定。显然,需要更大规模的研究以及功能研究来证实VEGF SNP在AMI及其AMI后并发症中的作用。

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