British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Pharmacol Ther. 2012 Oct;136(1):23-34. doi: 10.1016/j.pharmthera.2012.07.002. Epub 2012 Jul 14.
Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), including stent insertion, are established therapies in both acute coronary syndromes (ACS) and symptomatic chronic coronary artery disease refractory to pharmacological therapy. These continually advancing treatments remain limited by failure of conduit grafts in CABG and by restenosis or thrombosis of stented vessel segments in PCI caused by neointimal hyperplasia, impaired endothelialisation and accelerated atherosclerosis. While pharmacological and technological advancements have improved patient outcomes following both procedures, when grafts or stents fail these result in significant health burdens. In this review we discuss the pathophysiology of vein graft disease and in-stent restenosis, gene therapy vector development and design, and translation from pre-clinical animal models through human clinical trials. We identify the key issues that are currently preventing vascular gene therapy from interfacing with clinical use and introduce the areas of research attempting to overcome these.
冠状动脉旁路移植术（CABG）和经皮冠状动脉介入治疗（PCI），包括支架置入术，是急性冠状动脉综合征（ACS）和对药物治疗有反应的症状性慢性冠状动脉疾病的既定治疗方法。这些不断发展的治疗方法仍然受到 CABG 中移植物失败和 PCI 中支架血管段再狭窄或血栓形成的限制，这是由新生内膜增生、内皮化受损和动脉粥样硬化加速引起的。虽然药理学和技术进步改善了这两种治疗方法后的患者预后，但当移植物或支架失败时，这会导致严重的健康负担。在这篇综述中，我们讨论了静脉移植物疾病和支架内再狭窄的病理生理学、基因治疗载体的开发和设计，以及从临床前动物模型到人体临床试验的转化。我们确定了目前阻碍血管基因治疗与临床应用相结合的关键问题，并介绍了试图克服这些问题的研究领域。
