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载病毒载体基因治疗内膜增生和动脉粥样硬化猪再狭窄。

Delivery of viral vectors for gene therapy in intimal hyperplasia and restenosis in atherosclerotic swine.

机构信息

Department of Clinical and Translational Science, School of Medicine, Creighton University, Omaha, NE, 68178, USA.

Department of Clinical and Translational Science, The Peekie Nash Carpenter Endowed Chair in Medicine, School of Medicine, Creighton University, CRISS II Room 510, 2500 California Plaza, Omaha, NE, 68178, USA.

出版信息

Drug Deliv Transl Res. 2018 Aug;8(4):918-927. doi: 10.1007/s13346-017-0409-0.

Abstract

Cardiovascular diseases including atherosclerosis are a major financial and health burden globally. Inflammation associated with atherosclerosis results in the development of plaques that can rupture causing thrombosis, stroke, or death. The most widely used treatment for the removal of atherosclerotic plaques is percutaneous transluminal coronary angioplasty (PTCA) with or without stenting. Although this is a safer and minimally invasive method, restenosis and intimal hyperplasia after interventional procedure remains a major hurdle and more refined approaches are needed. Studies in large animal models such as pigs have facilitated a greater understanding of the underlying mechanisms of the disease and provided novel targets for therapeutic intervention. In pre-clinical studies, viral vector gene therapy has emerged as a promising option for the reduction and/or prevention of restenosis and intimal hyperplasia. Although studies in animal models have generated promising results, clinical trials have yet to prove the clinical efficacy of gene therapy in coronary artery diseases. In this review, we examined and critically reviewed the most recent advances in viral vector gene therapy obtained from studies using porcine model of atherosclerosis.

摘要

心血管疾病包括动脉粥样硬化是全球范围内的一个主要的经济和健康负担。与动脉粥样硬化相关的炎症导致斑块的形成,斑块破裂会导致血栓形成、中风或死亡。目前最广泛用于去除动脉粥样硬化斑块的治疗方法是经皮腔内冠状动脉血管成形术(PTCA),包括支架置入和不包括支架置入。尽管这是一种更安全、微创的方法,但介入治疗后的再狭窄和内膜增生仍然是一个主要的障碍,需要更精细的方法。在大型动物模型(如猪)中的研究促进了对疾病潜在机制的更深入理解,并为治疗干预提供了新的靶点。在临床前研究中,病毒载体基因治疗已成为减少和/或预防再狭窄和内膜增生的一种有前途的选择。尽管动物模型研究取得了有希望的结果,但临床试验尚未证明基因治疗在冠状动脉疾病中的临床疗效。在这篇综述中,我们检查并批判性地回顾了使用猪动脉粥样硬化模型获得的病毒载体基因治疗的最新进展。

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