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腺病毒介导的谷胱甘肽-S-转移酶过表达减轻兔颈动脉同种异体移植动脉硬化。

Adenovirus-mediated overexpression of glutathione-s-transferase mitigates transplant arteriosclerosis in rabbit carotid allografts.

机构信息

Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.

出版信息

Transplantation. 2010 Feb 27;89(4):409-16. doi: 10.1097/TP.0b013e3181c69838.

DOI:10.1097/TP.0b013e3181c69838
PMID:20177342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2861492/
Abstract

BACKGROUND

Cardiac transplant arteriosclerosis or cardiac allograft vasculopathy remains the leading cause of graft failure and patient death in heart transplant recipients. Endothelial cell injury is crucial in the development of human atherosclerosis and may play a role in allograft vasculopathy. Glutathione-S-transferase (GST) is known to protect endothelial cells from damage by oxidants and toxins. However, the contribution of human GST A4-4 (hGSTA4-4) to vascular cell injury and consequent transplant arteriosclerosis is unknown.

METHODS

A recombinant adenoviral vector containing hGSTA4-4 gene was constructed and delivered to vascular endothelial cells in an in vivo rabbit carotid artery transplant model. Forty-five days after transplantation, allografts were harvested (n=28). Blood flow was measured by ultrasonography. In addition, grafts were analyzed by histology, morphometry, immunostaining, and western blot.

RESULTS

The severity of arteriosclerosis in hGSTA4-4 transduced allografts was compared with control by measuring degree of stenosis by neointima. Decrease in blood flow in hGSTA4-4 transduced allografts was significantly less than control allografts, which also developed greater intimal thickening and stenosis than hGSTA4-4 transduced allografts in the proximal and distal regions of the graft. Leukocyte and macrophage infiltration was reduced in hGSTA4-4 transduced carotid arteries.

CONCLUSION

Our data indicate that hGSTA4-4 overexpression protects the integrity of vessel wall from oxidative injury, and attenuates transplant arteriosclerosis.

摘要

背景

心脏移植后发生的动脉硬化或同种异体移植血管病仍是导致移植物衰竭和患者死亡的首要原因。内皮细胞损伤在人类动脉粥样硬化的发生发展中起关键作用，可能在移植后血管病中发挥作用。谷胱甘肽-S-转移酶（GST）可保护内皮细胞免受氧化剂和毒素的损伤。然而，人 GST A4-4（hGSTA4-4）对血管细胞损伤和随后的移植后动脉硬化的贡献尚不清楚。

方法

构建了含有 hGSTA4-4 基因的重组腺病毒载体，并将其递送至体内兔颈动脉移植模型中的血管内皮细胞。移植后 45 天，收获同种异体移植物（n=28）。通过超声测量血流。此外，通过组织学、形态计量学、免疫染色和 Western blot 分析移植物。

结果

通过测量新生内膜的狭窄程度，比较 hGSTA4-4 转导的同种异体移植物与对照组的动脉硬化严重程度。hGSTA4-4 转导的同种异体移植物的血流量下降明显低于对照组，并且在移植物的近端和远端区域，hGSTA4-4 转导的同种异体移植物的内膜增厚和狭窄程度也大于对照组。hGSTA4-4 转导的颈动脉中的白细胞和巨噬细胞浸润减少。

结论

我们的数据表明 hGSTA4-4 过表达可保护血管壁的完整性免受氧化损伤，并减轻移植后动脉硬化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/3837ee098a53/nihms-167017-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/f36b201a7f7c/nihms-167017-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/29c390c5adc5/nihms-167017-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/54e32d39383e/nihms-167017-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/9d3fb311879d/nihms-167017-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/230ba2fdb834/nihms-167017-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/3837ee098a53/nihms-167017-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/f36b201a7f7c/nihms-167017-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/29c390c5adc5/nihms-167017-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/54e32d39383e/nihms-167017-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/9d3fb311879d/nihms-167017-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/230ba2fdb834/nihms-167017-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0f/2861492/3837ee098a53/nihms-167017-f0006.jpg

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3
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