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基因治疗在旁路移植血管内膜增生中的作用。

The role of gene therapy for intimal hyperplasia of bypass grafts.

作者信息

Cable D G, Caccitolo J A, Caplice N, O'Brien T, Simari R D, Daly R C, Dearani J A, Mullany C J, Orszulak T A, Schaff H V

机构信息

Division of Thoracic and Cardiovascular Surgery, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.

出版信息

Circulation. 1999 Nov 9;100(19 Suppl):II392-6. doi: 10.1161/01.cir.100.suppl_2.ii-392.

DOI:10.1161/01.cir.100.suppl_2.ii-392
PMID:10567335
Abstract

BACKGROUND

Proliferation of the intima is an early lesion of saphenous vein graft disease. Early patency rates of radial artery grafts are acceptable, but little is known about their risk of intimal hyperplasia.

METHODS AND RESULTS

To develop a model of intimal hyperplasia, we incubated human saphenous veins, internal mammary arteries, and radial arteries (n=6, 8, and 10, respectively) in an organ culture with Roswell Park Memorial Institute 1640 (30% serum) for 0, 4, 7, 10, and 14 days. Quantitative histological studies were performed, and the average intimal-to-medial (I/M) ratio was calculated for each incubation interval. After 10 and 14 days of culture, the I/M ratio increased in the saphenous veins (P=0. 03, P=0.04 versus 0 day, respectively). No significant increase occurred in the I/M ratio in either the internal mammary or radial arteries. Next, the ability of adenoviral gene transfers to inhibit intimal hyperplasia in the saphenous veins was evaluated. Adenoviral-mediated gene transfer of nitric oxide synthase significantly reduced the I/M ratio at 14 days compared with vehicle (P=0.001) and virus (P=0.004) controls.

CONCLUSIONS

The human saphenous vein has a greater propensity for intimal hyperplasia than arterial grafts; the human radial artery behaves similarly to the internal mammary artery. In the future, gene therapy may augment nitric oxide synthase, limiting vein graft disease.

摘要

背景

内膜增殖是隐静脉移植血管病变的早期损害。桡动脉移植血管的早期通畅率尚可,但关于其内膜增生风险的了解甚少。

方法与结果

为建立内膜增生模型,我们将人隐静脉、乳内动脉和桡动脉(分别为n = 6、8和10)置于含有罗斯韦尔帕克纪念研究所1640培养基(30%血清)的器官培养体系中培养0、4、7、10和14天。进行定量组织学研究,并计算每个培养时间间隔的平均内膜与中膜(I/M)比值。培养10天和14天后,隐静脉的I/M比值升高(分别与0天相比,P = 0.03,P = 0.04)。乳内动脉和桡动脉的I/M比值均未显著升高。接下来,评估腺病毒基因转移抑制隐静脉内膜增生的能力。与载体对照组(P = 0.001)和病毒对照组(P = 0.004)相比,腺病毒介导的一氧化氮合酶基因转移在14天时显著降低了I/M比值。

结论

人隐静脉比动脉移植血管更易发生内膜增生;人桡动脉的表现与乳内动脉相似。未来,基因治疗可能会增强一氧化氮合酶,限制静脉移植血管病变。

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