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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:224.)
© 2006 American Heart Association, Inc.

Thrombosis

Adiponectin Acts as an Endogenous Antithrombotic Factor

Hisashi Kato; Hirokazu Kashiwagi; Masamichi Shiraga; Seiji Tadokoro; Tsuyoshi Kamae; Hidetoshi Ujiie; Shigenori Honda; Shigeki Miyata; Yoshinobu Ijiri; Junichiro Yamamoto; Norikazu Maeda; Tohru Funahashi; Yoshiyuki Kurata; Iichiro Shimomura; Yoshiaki Tomiyama; Yuzuru Kanakura

From the Departments of Hematology and Oncology (H. Kato, H. Kashiwagi, M.S., S.T., T.K., H.U., Y.T., Y.Ka.) and Internal Medicine and Molecular Science (N.M., T.F., I.S.), Graduate School of Medicine, Osaka University, Suita; National Cardiovascular Center Research Institute (S.H.), Suita, Osaka; Division of Transfusion Medicine (S.M.), National Cardiovascular Center, Suita, Osaka; Department of Nutrition Management (Y.I.), Faculty of Health Science, Hyogo University, Kakogawa, Hyogo; Laboratory of Physiology, Faculty of Nutrition (J.Y.) and High Technology Research Centre (J.Y.), Kobe Gakuin University, Kobe; and Department of Blood Transfusion (Y.Ku.), Osaka University Hospital, Suita, Japan.

Correspondence to Yoshiaki Tomiyama, Osaka University, Department of Hematology and Oncology, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail yoshi{at}hp-blood.med.osaka-u.ac.jp

Objective— Obesity is a common risk factor in insulin resistance and cardiovascular diseases. Although hypoadiponectinemia is associated with obesity-related metabolic and vascular diseases, the role of adiponectin in thrombosis remains elusive.

Methods and Results— We investigated platelet thrombus formation in adiponectin knockout (APN-KO) male mice (8 to 12 weeks old) fed on a normal diet. There was no significant difference in platelet counts or coagulation parameters between wild-type (WT) and APN-KO mice. However, APN-KO mice showed an accelerated thrombus formation on carotid arterial injury with a He-Ne laser (total thrombus volume: 13.36±4.25x10⁷ arbitrary units for APN-KO and 6.74±2.87x10⁷ arbitrary units for WT; n=10; P<0.01). Adenovirus-mediated supplementation of adiponectin attenuated the enhanced thrombus formation. In vitro thrombus formation on a type I collagen at a shear rate of 250 s^–1, as well as platelet aggregation induced by low concentrations of agonists, was enhanced in APN-KO mice, and recombinant adiponectin inhibited the enhanced platelet aggregation. In WT mice, adenovirus-mediated overexpression of adiponectin additionally attenuated thrombus formation.

Conclusion— Adiponectin deficiency leads to enhanced thrombus formation and platelet aggregation. The present study reveals a new role of adiponectin as an endogenous antithrombotic factor.

We demonstrated an enhanced thrombus formation and platelet aggregation in adiponectin knockout mice and that adenovirus-mediated supplementation of adiponectin attenuated the enhanced thrombus formation. In wild-type mice, overexpression of adiponectin attenuated thrombus formation. These findings reveal a new role of adiponectin as an endogenous antithrombotic factor.

Key Words: acute coronary syndromes • obesity • platelets • thrombosis

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