Long term evaluation of coronary bypass with vein grafts transfered with CNP gene

转CNP基因静脉移植冠状动脉搭桥术的长期评价

• 批准号: 14571263
• 负责人: IKEDA Tadashi
• 金额: $ 2.05万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571263/
• 关键词: Coronary bypass; Atherosclerosis; Vein graft; Natriuretic peptide; 遺伝子導入; アデノウイルス

C-type natriuretic peptide (CNP) acts toward relaxation and growth inhibition of vascular smooth muscle cells (VSMC) via activation of selective receptor, ANP-B receptor. We have developed a replication deficient adenoviral vector overexpressing CNP gene (Ad.CNP), and reported that this vector potently inhibits proliferation of cultured VSMC. In this study, using balloon injury model of rabbit carotid artery, we revealed that topical overexpression of CNP gene after injury markedly inhibits neointimal proliferation after endothelial injury in vivo. Moreover, redifferentiation of VSMC and regeneration of endothelial cells were observed in the neointima treated with Ad.CNP. We then examined effects of CNP overexpression on autologous vein grafts. Rabbit jugular vein treated with Ad.CNP or control vector ex vivo were interposed into carotid artery. In veins treated with Ad.CNP, tissue concentration of CNP and cGMP were elevated and inhibition of neointimal thickening, inhibition of early and late thrombosis and promotion of endothelial regeneration were observed. Based on these findings, we tried to develop coronary bypass graft model using internal mammary artery and hind limb vein of beagle. However, mainly because of technical difficulties, we failed to establish the model to evaluate long-term evaluation of the grafts.

C型利钠肽(CNP)通过激活选择性受体ANP-B受体，起到松弛和抑制血管平滑肌细胞(VSMC)生长的作用。我们研制了一种高表达CNP基因的复制缺陷腺病毒载体(Ad.CNP)，并报道了该载体能有效地抑制培养的VSMC的增殖。本研究采用兔颈动脉球囊损伤模型，发现损伤后局部过表达CNP基因可明显抑制血管内皮损伤后新生内膜的增殖。此外，在Ad.CNP处理的新生内膜中观察到VSMC的再分化和内皮细胞的再生。然后，我们观察了CNP过表达对自体静脉移植物的影响。将经Ad.CNP处理的兔颈静脉或体外对照载体插入颈动脉。静脉注射Ad.CNP后，组织中CNP和cGMP浓度升高，抑制新生内膜增厚，抑制早期和晚期血栓形成，促进血管内皮细胞再生。在此基础上，我们尝试建立了Beagle犬乳内动脉和后肢静脉冠状动脉搭桥模型。然而，主要是由于技术上的困难，我们未能建立模型来评价移植物的长期评价。

项目成果

Ohno et al.: "Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide."Circulation. 105. 1623-1626 (2002)

Ohno等人：“通过腺病毒介导的C型利钠肽基因转移，加速再内皮化，抑制兔颈静脉移植物的血栓形成特性和新内膜增生。”循环。

N. Ohno, et al.: "Accelerated re-endothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide"Circulation. 105. 1623-1626 (2002)

N. Ohno 等人：“通过腺病毒介导的 C 型钠尿肽基因转移，加速再内皮化，抑制兔颈静脉移植物的血栓形成特性和新生内膜增生”。

池田 義ほか: "微小冠動脈に対する新しい血行再建法"Bio-CABG"の実験的検討"Progress in Medicine. 23(7). 1768-1772 (2003)

Yoshi Ikeda 等人：“微冠状动脉新血运重建方法“Bio-CABG”的实验研究”医学进展 23(7) (2003)。