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- Title
TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival.
- Authors
Gang Chen; Qin Wei; Xi-Mo Wang, Leo H.; Wan-Yu Wang, Leo H.; Yu-Liang Xiong, Leo H.; Shi Chen
- Abstract
Chen G, Wei Q, Wang X-M, Wang W-Y, Xiong Y-L, Chen S. TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi formation and prolongs discordant cardiac xenograft survival. Xenotransplantation 2004; 11: 203–209. © Blackwell Munksgaard, 2004 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 μg/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 μg/kg, i.v., 0.5 h before reperfusion). Additionally, levels of TXB2 and 6-keto-PGF1α within rejected graft tissues were determined by radioimmunoassay. Treatment with TMVA at a dose of 20 or 40 μg/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-PGF1α 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 PGI2/TXA2 in TMVA treatment group may protect xenografts from the endothelial cell activation and contribute to the prolongation of xenograft survival.
- Subjects
GLYCOPROTEINS; TRIMERESURUS; BLOOD platelet aggregation; TRANSPLANTATION of organs, tissues, etc.; PROTEIN binding; XENOGRAFTS
- Publication
Xenotransplantation, 2004, Vol 11, Issue 2, p203
- ISSN
0908-665X
- Publication type
Article
- DOI
10.1111/j.1399-3089.2003.00114.x