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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3461-3468.)
© 1997 American Heart Association, Inc.

Articles

Triflavin Inhibits Platelet-Induced Vasoconstriction in De-endothelialized Aorta

J.-R. Sheu; M. H. Yen; W. C. Hung; Y. M. Lee; C. H. Su; ; T. F. Huang

From the Graduate Institute of Medical Sciences, Taipei Medical College (J.-R.S., W.C.H., C.H.S.), the Department of Pharmacology, National Defense Medical Center (M.H.Y., Y.M.L.), and the Institute of Pharmacology, Medical College, National Taiwan University (T.F.H.), Taipei, Taiwan.

Correspondence to Dr Joen-Rong Sheu, Graduate Institute of Medical Sciences, Taipei Medical College, No. 250, Wu-Hsing St, Taipei, Taiwan.

Abstract Triflavin, a 7.5-kD cysteine-rich polypeptide purified from Trimeresurus favoviridis snake venom, belongs to a family of Arg-Gly-Asp-(RGD)–containing peptides, termed disintegrins. In this study, aggregating human platelets dose- dependently induced vasoconstriction in de-endothelialized isolated rat thoracic aortas. At 5x10⁷ cells per milliliter, platelets induced a peak tension averaging 65±7.2% of the tension induced by phenylephrine (10 µmol/L). The relative effectiveness of RGD-containing peptides (including venom peptides triflavin and trigramin, small RGD synthetic peptides Gly-Arg-Gly-Asp-Ser [GRGDS], Gly-Arg-Gly-Asp-Phe [GRGDF], and Gly-Arg-Gly-Asp-Ser-Pro-Lys [GRGDSPK]) was examined by testing the inhibitory effect on aggregating platelet-induced vasoconstriction in de-endothelialized aorta. Triflavin (1 µmol/L) significantly inhibited the platelet-induced vasoconstriction, whereas neither trigramin (10 µmol/L) nor small RGD peptides (2 mmol/L) (ie, GRGDS, GRGDF, and GRGDSPK) showed any significant effect. The release of serotonin and the formation of thromboxane A₂ from aggregating platelets were both significantly inhibited by triflavin (2 µmol/L), whereas trigramin and small RGD-containing peptides showed no significant effect. On scanning electron micrographs of de-endothelialized aorta, aggregating platelets adhered to the subendothelium, with loss of their discoid shape, to form irregular spheres with pseudopod extensions. Triflavin (2 µmol/L) markedly reduced the adhesion of platelets to the subendothelium in the same aorta. Furthermore, RGD-containing peptides (including triflavin, trigramin, and small RGD-containing peptides) inhibited the adhesion of 10 µg/mL collagen-activated platelets to extracellular matrices (ie, fibronectin, vitronectin, and von Willebrand factor). It is concluded that the marked ability of triflavin to inhibit aggregating platelet-induced vasoconstriction in de-endothelialized aorta compared with other RGD-containing peptides (including trigramin), may be due at least partly to triflavin's efficiently preventing the activation of platelets subsequent to inhibition of serotonin release and thromboxane A₂ formation. However, the different abilities of triflavin compared with other RGD-containing peptides was not related to the ability to inhibit adhesion of platelets to extracellular matrices. Therefore, from the results of this study, it appears that triflavin may be a useful therapeutic agent for the treatment of thromboembolism and its associated angiospasm.

Key Words: RGD-containing peptides • triflavin • de-endothelialization • serotonin • thromboxanes

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