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[基因治疗用于冠状动脉成形术后再狭窄的治疗]

[Gene therapy for the treatment of restenosis after coronary angioplasty].

作者信息

Rapacciuolo A, Indolfi C, Di Lorenzo E, Esposito G, Stabile E, Stingone A M, Avvedimento E V, Condorelli M, Chiariello M

机构信息

Cattedra di Cardiologia, Università degli Studi Federico II, Napoli.

出版信息

Cardiologia. 1994 Dec;39(12):843-7.

PMID:7781002
Abstract

Accumulation and proliferation of vascular smooth muscle cells are associated with atherosclerosis and hypertension. Proliferation of smooth muscle cells constitutes a major pathological event responsible for long-term failure of coronary and peripheral arterial bypass graft as well as the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The incidence of restenosis after PTCA has been reported to be as high as 40-45% within 3-6 months. Major advantages in recombinant deoxyribonucleic acid (DNA) technology and eukaryotic gene regulation allow to hypothesize gene therapy as a potential treatment for inherited and acquired diseases. Gene therapy is the introduction of genes into somatic cells to correct an inherited or acquired disorder through the synthesis of missing or defective protein. Although no disease has yet been treated by gene therapy, several gene transfer protocols have recently been undertaken. We have studied the expression of foreign DNA that has been introduced into smooth muscle cells after balloon carotid injury in a rat model of angioplasty. The effects of different degree of balloon injury on neointima formation and c-fos expression was also assessed. Our data demonstrate that site-specific gene expression can be achieved by direct gene transfer in vivo and could be applied to the treatment of restenosis after PTCA.

摘要

血管平滑肌细胞的积聚和增殖与动脉粥样硬化和高血压相关。平滑肌细胞的增殖是导致冠状动脉和外周动脉旁路移植长期失败以及经皮腔内冠状动脉成形术(PTCA)后再狭窄发生的主要病理事件。据报道,PTCA后3至6个月内再狭窄的发生率高达40 - 45%。重组脱氧核糖核酸(DNA)技术和真核基因调控的主要优势使得人们能够设想基因治疗作为一种治疗遗传性和获得性疾病的潜在方法。基因治疗是将基因导入体细胞,通过合成缺失或有缺陷的蛋白质来纠正遗传性或获得性疾病。尽管尚未有疾病通过基因治疗得到治愈,但最近已经开展了几种基因转移方案。我们在大鼠血管成形术模型中研究了球囊损伤颈动脉后导入平滑肌细胞的外源DNA的表达情况。还评估了不同程度的球囊损伤对新生内膜形成和c - fos表达的影响。我们的数据表明,通过体内直接基因转移可以实现位点特异性基因表达,并且可应用于PTCA后再狭窄的治疗。

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