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缺血性心脏病中的治疗性血管生成:基因治疗还是重组血管生长因子蛋白治疗?

Therapeutic angiogenesis in ischemic heart disease: gene or recombinant vascular growth factor protein therapy?

作者信息

Kastrup Jens

机构信息

Medical Department B, Cardiac Catheterization Laboratory, The Heart Centre, University Hospital, Rigshospitalet, Copenhagen, Denmark.

出版信息

Curr Gene Ther. 2003 Jun;3(3):197-206. doi: 10.2174/1566523034578366.

Abstract

In the last decennium the challenge to research has been to find methods of inducing new vascular growth in ischemic myocardium due to atherosclerotic coronary artery disease, which could not be treated with balloon angioplasty or coronary artery by-pass grafting. Therapeutic angiogenesis with recombinant vascular endothelial growth factor proteins or gene encoding for the proteins is a new potential treatment for cardiovascular disease. The greatest interest and research has been concentrated on basic Fibroblast Growth Factor (FGF1 and FGF2) and Vascular Endothelial Growth Factor A (VEGF-A165 and VEGF-A121). Several small clinical phase I-II safety and efficacy trials with recombinant vascular endothelial growth factor proteins or gene encoding for the proteins have demonstrated that these treatment regimes seem to be safe and the results have been encouraging. However, two large doubleblind randomized placebo-controlled studies with intracoronary infusions of the recombinant proteins FGF2 and VEGF-A165 could not detect any clinical effect. Large scaled phase II studies with gene therapy are in progress. Therapeutic angiogenesis is still a promising new treatment in patients with coronary artery disease. However, more research including large scaled clinical trials is needed before deciding whether the vascular endothelial growth factor therapy either as a gene or a recombinant slow-release protein formulation therapy can be offered to patients with severe coronary artery disease, which cannot be treated with conventional revascularization.

摘要

在过去十年中,研究面临的挑战是找到在因动脉粥样硬化性冠状动脉疾病导致的缺血心肌中诱导新血管生长的方法,这类疾病无法通过球囊血管成形术或冠状动脉搭桥术进行治疗。使用重组血管内皮生长因子蛋白或编码这些蛋白的基因进行治疗性血管生成是心血管疾病的一种新的潜在治疗方法。最大的兴趣和研究集中在碱性成纤维细胞生长因子(FGF1和FGF2)以及血管内皮生长因子A(VEGF - A165和VEGF - A121)上。几项关于重组血管内皮生长因子蛋白或编码这些蛋白的基因的小型临床I - II期安全性和有效性试验表明,这些治疗方案似乎是安全的,结果令人鼓舞。然而,两项关于冠状动脉内输注重组蛋白FGF2和VEGF - A165的大型双盲随机安慰剂对照研究未能检测到任何临床效果。基因治疗的大规模II期研究正在进行中。治疗性血管生成对于冠状动脉疾病患者仍然是一种有前景的新治疗方法。然而,在决定是否可以将血管内皮生长因子疗法作为基因疗法或重组缓释蛋白制剂疗法提供给无法通过传统血运重建治疗的严重冠状动脉疾病患者之前,还需要进行更多的研究,包括大规模临床试验。

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