Triflavin Inhibits Platelet-Induced Vasoconstriction in De-endothelialized Aorta

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 17; no. 12; pp. 3461 - 3468
• Main Authors: Sheu, J.-R, Yen, M.H, Hung, W.C, Lee, Y.M, Su, C.H, Huang, T.F
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-12-1997; Hagerstown, MD Lippincott
• Subjects: Animals; Aorta - physiology; Biological and medical sciences; Blood Platelets - physiology; Cardiovascular system; Cell Adhesion - drug effects; Collagen - metabolism; Crotalid Venoms - pharmacology; Disintegrins - pharmacology; Endothelium, Vascular - physiology; Extracellular Matrix Proteins - metabolism; Female; Humans; Male; Medical sciences; Microscopy, Electron, Scanning; Oligopeptides - pharmacology; Peptides - pharmacology; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Rats; Rats, Sprague-Dawley; Serotonin - metabolism; Serotonin - physiology; Thromboxane B2 - metabolism; Vascular wall; Vasoconstriction - drug effects; Human; Rat; Rodentia; Alteration; Animal origin; Cardiovascular disease; Anticoagulant; Endothelium; Vascular disease; Vertebrata; Chemotherapy; Platelet; Mammalia; Integrin; Treatment; Antispasmodic agent; Induced vasoconstriction; Animal; Venom; Aorta; Inhibition; Mechanism of action; Thromboembolism
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.atv.17.12.3461

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 5 x 10 cells per milliliter, platelets induced a peak tension averaging 65 +/- 7.2% of the tension induced by phenylephrine (10 micro mol/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 micro mol/L) significantly inhibited the platelet-induced va-soconstriction, whereas neither trigramin (10 micro mol/L) nor small RGD peptides (2 micro mol/L) (ie, GRGDS, GRGDF, and GRGD-SPK) showed any significant effect. The release of serotonin and the formation of thromboxane A2 from aggregating platelets were both significantly inhibited by triflavin (2 micro mol/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 micro mol/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 micro gram/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. (Arterioscler Thromb Vasc Biol. 1997;17:3461-3468.)