TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival

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	TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival
	Chen G 1; Wei Q 2; Wang XM 1; Wang WY 2; Xiong YL 2; Chen S*1; schen@tjh.tjmu.edu.cn
	2004
发表期刊	XENOTRANSPLANTATION
ISSN	0908-665X
卷号	11 期号:2 页码:203-209
合作性质	其它
摘要	In xenotransplantation, donor endothelium is the first target of immunological attack. Activation of the endothelial cell by preformed natural antibodies leads to platelet binding via the interaction of the glycoprotein (GP) Ib and von Willebrand factor (vWF). TMVA is a novel GPIb-binding protein purified from the venom of Trimeresurus mucrosquamatus. In this study, the inhibitory effect of TMVA on platelet aggregation in rats and the effect on discordant guinea pig-to-rat cardiac xenograft survival were investigated. Three doses (8, 20 or 40 mug/kg) of TMVA were infused intravenously to 30 rats respectively. Platelet aggregation rate was assayed 0.5, 12, and 24 h after TMVA administration. Wister rats underwent guinea pig cardiac cervical heterotopic transplantation using single dosing of TMVA (20 mug/kg, i.v., 0.5 h before reperfusion). Additionally, levels of TXB2 and 6-keto-PGF(1alpha) within rejected graft tissues were determined by radioimmunoassay. Treatment with TMVA at a dose of 20 or 40 mug/kg resulted in complete inhibition of platelet aggregation 0.5 h after TMVA administration. Rats receiving guinea pig cardiac xenografts after TMVA therapy had significantly prolonged xenograft survival. Histologic and immunopathologic analysis of cardiac xenografts in TMVA treatment group showed no intragraft platelet microthrombi formation and fibrin deposition. Additionally, the ratio of 6-keto-PGF(1alpha) to TXB2 in TMVA treatment group was significantly higher than those in control group. We conclude that the use of this novel GPIb-binding protein was very effective in preventing platelet microthrombi formation and fibrin deposition in a guinea pig-to-rat model and resulted in prolongation of xenograft survival. The increased ratio of PGI(2)/TXA(2) in TMVA treatment group may protect xenografts from the endothelial cell activation and contribute to the prolongation of xenograft survival.
关键词	Glycoprotein (Gp) Ib Platelet Aggregation Tmva Trimeresurus Mucrosquamatus Xenotransplantation
资助者	This study was supported by a grant of ‘National Natural Science Foundation of China (39993434)’ and by ‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’. ; This study was supported by a grant of ‘National Natural Science Foundation of China (39993434)’ and by ‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’. ; This study was supported by a grant of ‘National Natural Science Foundation of China (39993434)’ and by ‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’. ; This study was supported by a grant of ‘National Natural Science Foundation of China (39993434)’ and by ‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’.
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收录类别	SCI
语种	英语
资助者	This study was supported by a grant of ‘National Natural Science Foundation of China (39993434)’ and by ‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’. ; This study was supported by a grant of ‘National Natural Science Foundation of China (39993434)’ and by ‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’. ; This study was supported by a grant of ‘National Natural Science Foundation of China (39993434)’ and by ‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’. ; This study was supported by a grant of ‘National Natural Science Foundation of China (39993434)’ and by ‘the National High Technology Research and Development Program (863 program) of China (101-05-05-01)’.
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/5327
专题	其他
通讯作者	schen@tjh.tjmu.edu.cn
作者单位	1.Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2.Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
推荐引用方式 GB/T 7714	Chen G,Wei Q,Wang XM,et al. TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival[J]. XENOTRANSPLANTATION,2004,11(2):203-209.
APA	Chen G.,Wei Q.,Wang XM.,Wang WY.,Xiong YL.,...&schen@tjh.tjmu.edu.cn.(2004).TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival.XENOTRANSPLANTATION,11(2),203-209.
MLA	Chen G,et al."TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival".XENOTRANSPLANTATION 11.2(2004):203-209.

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