Anopheline anti-platelet protein from a malaria vector mosquito has anti-thrombotic effects in vivo without compromising hemostasis

• Published in: Thrombosis research 2012-02, Vol.129 (2), p.169-175
• Main Authors: Hayashi, Hideki, Kyushiki, Hiroyuki, Nagano, Keisuke, Sudo, Toshiki, Matsuoka, Hiroyuki, Yoshida, Shigeto
• Format: Article
• Language: English
• Subjects: Animals; Anopheles - metabolism; anti-platelet agents; Biological and medical sciences; bleeding; Blood and lymphatic vessels; Blood Coagulation - drug effects; Blood coagulation. Blood cells; Cardiology. Vascular system; collagen; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Fibrinolytic Agents - therapeutic use; Fundamental and applied biological sciences. Psychology; Hematology, Oncology and Palliative Medicine; Hemostasis - drug effects; Insect Proteins - therapeutic use; Medical sciences; Mice; Mice, Inbred ICR; Molecular and cellular biology; mosquito; Platelet; Platelet Activation - drug effects; platelet aggregation; Platelet Aggregation Inhibitors - therapeutic use; Pulmonary Embolism - drug therapy; Pulmonary Embolism - physiopathology; salivary gland; Salivary Glands - secretion; Treatment Outcome
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2011.09.015

Abstract Introduction The saliva of blood-feeding animals (e.g., mosquitoes, ticks, bats) has pharmacological activities that facilitate efficient blood-sucking. We previously identified a unique anti-platelet protein, anopheline anti-platelet protein (AAPP), from the salivary gland of female Anopheles stephensi (human malaria vector mosquito). AAPP specifically blocks platelet adhesion to collagen by binding directly to collagen and subsequently aggregating platelets. To examine the potential of AAPP as a therapeutic agent, we investigated the in vivo anti-thrombotic effects of AAPP. Materials and Methods Effects of AAPP on whole blood/platelet aggregation in mice were examined. AAPP was also challenged in an established model of pulmonary thromboembolism in mice. We simultaneously investigated the side-effects of the protein (prolongation of bleeding time and coagulation time). Aspirin was used as a positive control for comparison of anti-thrombotic effects. Results and Conclusions AAPP inhibited whole blood aggregation induced by collagen at 10 mg/kg body weight. AAPP prevented pulmonary death at a lower dose (3 mg/kg) without prolongation of bleeding time compared with aspirin (100 mg/kg) that compromised hemostasis. AAPP and aspirin did not affect coagulation time. These results indicate that AAPP has great potential as a new anti-platelet agent with a better risk/benefit ratio than that seen with aspirin (the most widely used anti-platelet agent).