Inhibition of smooth muscle cell migration and neointima formation in vein grafts by overexpression of matrix metalloproteinase-3.
Inhibition of smooth muscle cell migration and neointima formation in vein grafts by overexpression of matrix metalloproteinase-3.
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DOI：
10.1016/j.jvs.2008.11.001
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发表时间：
2009-03
影响因子：
4.3
通讯作者：
Haverich, Axel
中科院分区：
文献类型：
--
作者：
Kallenbach, Klaus;Salcher, Rolf;Heim, Albert;Karck, Matthias;Mignatti, Paolo;Haverich, Axel
大隐静脉移植物在旁路手术后遭受新内膜形成。基质金属蛋白酶（MMPs）在这一过程中发挥了重要作用。我们使用腺病毒介导的基因转移检测了MMP-3在静脉旁路移植物中预防平滑肌细胞迁移和新生内膜形成的治疗潜力。用编码β-半乳糖苷酶（Ad. β gal）或人MMP-3（Ad. hMMP-3）的腺病毒载体转导人主动脉平滑肌细胞（hAoSMC），并表征其在羊膜基质中的迁移，作为血管壁的体外模型。胆固醇喂养的新西兰白色兔接受颈静脉旁路移植术进入颈动脉。在插入之前，将移植物与Ad. β gal或Ad. hMMP-3离体孵育。转基因表达的特点是免疫组织化学和原位酶谱。移植物（n = 6）在28天后取出，并对内膜增生进行定量。与对照相比，当用Ad. hMMP-3转导时，hAoSMC的迁移显著减少（p <0.001）。Ad. hMMP-3转导的静脉移植物的免疫细胞化学将该蛋白定位于内膜。原位酶谱显示Ad. hMMP-3转染的移植物内膜中MMP活性增加。与对照组相比，在用Ad. MMP-3转导的移植物中狭窄程度（p = 0.001）、内膜/中膜比率（p = 0.023）和病变厚度（p = 0.003）显著降低。对照组内无差异。MMP-3过表达抑制动脉化静脉移植物内膜增生的形成腺病毒介导的MMP-3基因转移可能用于预防旁路手术后静脉移植物狭窄的临床应用。
Saphenous vein grafts suffer from neointima formation following bypass surgery. Matrix metalloproteinases (MMPs) play important roles in this process. We examined MMP-3 for its therapeutic potential to prevent smooth muscle cell migration and neointima formation in venous bypass grafts using adenovirus-mediated gene transfer. Human aortic smooth muscle cells (hAoSMC) were transduced with adenoviral vectors encoding β-galactosidase (Ad.βgal) or human MMP-3 (Ad.hMMP-3), and characterized for migration in the amniotic membrane stroma as an in vitro model of the vascular wall. Cholesterol-fed New Zealand White rabbits underwent jugular vein bypass grafting into carotid arteries. Before insertion, grafts were incubated ex vivo with either Ad.βgal or Ad.hMMP-3. Transgene expression was characterized by immunohistochemistry and in situ zymography. Grafts (n=6) were explanted after 28 days and intimal hyperplasia was quantified. Migration of hAoSMC was significantly reduced when transduced with Ad.hMMP-3 compared to controls (p<0.001). Immunocytochemistry of Ad.hMMP-3 transduced venous grafts localized this protein to the intima. In situ-zymography showed increased MMP activity in the intima of Ad.hMMP-3 transfected grafts. Stenosis degree (p=0,001), intima/media-ratio (p=0,023) and lesion thickness (p=0,003) were significantly reduced in grafts transduced with Ad.MMP-3 in comparison to controls. There was no difference inside control groups. MMP-3 overexpression inhibits formation of intimal hyperplasia in arterialized vein grafts. Adenovirus mediated gene transfer of MMP-3 may be of clinical use to prevent vein graft stenosis following bypass surgery.
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影响因子：
15.9
作者：
GALIS, ZS;SUKHOVA, GK;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
3.8
作者：
Fernandez, HA;Kallenbach, K;Galloway, AC
通讯作者：
Galloway, AC
DOI：
10.1073/pnas.0506201102
发表时间：
2005-10-25
影响因子：
11.1
作者：
Johnson, JL;George, SJ;Jackson, CL
通讯作者：
Jackson, CL
影响因子：
2
作者：
Lövdahl, C;Thyberg, J;Hultgårdh-Nilsson, A
通讯作者：
Hultgårdh-Nilsson, A
DOI：
10.1016/0735-1097(96)00206-9
发表时间：
1996-09-01
影响因子：
24
作者：
FitzGibbon, GM;Kafka, HP;Burton, JR
通讯作者：
Burton, JR