Gene therapy for vein grafts.
Gene therapy for vein grafts.
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DOI：
10.1007/s11886-000-0022-5
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发表时间：
2000-01-01
影响因子：
3.7
通讯作者：
Mann, M J
中科院分区：
文献类型：
--
作者：
Mann, M J
旁路静脉移植失败是目前心肌和下肢缺血手术治疗的最大限制。对内膜增生和随后的静脉移植动脉粥样硬化的分子和细胞生物学的阐明为设计和实施预防静脉移植疾病的基因疗法奠定了基础。操纵血管细胞周期进程的基因调控已被证明可以有效地将静脉移植物生物学从新内膜疾病转向内侧肥大，作为响应动脉循环压力的更具适应性的重塑形式，并预防实验性移植物动脉粥样硬化。早期临床经验表明，这种方法可能为在人类中转化这种基于基因的疗法提供早期途径。在静脉移植的动物模型中也探索了其他实验性基因转移策略，鉴于在疾病发生时直接接触组织，这可能特别适合基因操作的应用。
Bypass vein graft failure represents the greatest limitation to the current surgical therapy of myocardial and lower extremity ischemia. Elucidation of the molecular and cellular biology of neointimal hyperplasia and subsequent vein graft atherosclerosis has formed a basis for the design and implementation of gene-based therapies to prevent vein graft disease. Manipulation of the genetic regulation of vascular cell cycle progression has been shown to effectively redirect vein graft biology away from neointimal disease and toward medial hypertrophy as a more adaptive form of remodeling in response to stresses of the arterial circulation, and has prevented experimental graft atherosclerosis. Early clinical experience suggests that this approach may provide an early avenue for translation of such a gene-based therapy in humans. Other experimental gene transfer strategies have also been explored in animal models of vein grafts, which may be particularly well suited to the application of genetic manipulation given the direct access to the tissue at the time of disease initiation.