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(Circulation Research. 2001;89:1240.)
© 2001 American Heart Association, Inc.

Integrative Physiology

Recombinant Annexin II Modulates Impaired Fibrinolytic Activity In Vitro and in Rat Carotid Artery

Hideto Ishii, Masayuki Yoshida, Megumi Hiraoka, Katherine A. Hajjar, Akira Tanaka, Yukio Yasukochi, Fujio Numano

From the Department of Medicine (H.I., A.T., F.N.), School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; Department of Applied Genetics (M.Y., M.H., Y.Y.), Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; and Department of Pediatrics and Medicine (K.A.H.), Weill Medical College of Cornell University, New York, NY.

Correspondence to Masayuki Yoshida, MD, Department of Applied Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima Bldg D-621, Bunkyo-ku, Tokyo 113-8510. E-mail masamgen{at}mri.tmd.ac.jp

Fibrinolytic activity has been reported to be decreased in atherosclerosis. Recently, annexin II was identified as a coreceptor on endothelial cells for plasminogen and tissue plasminogen activator. In this study, we examined whether recombinant annexin II (rAN II) protein can modulate fibrinolytic activity on vascular endothelium in vitro and in vivo. The effect of rAN II on human umbilical vein endothelial cells (HUVECs) was measured. Addition of a fluorescent plasmin substrate revealed that HUVECs treated with rAN II exhibited significantly more plasmin generation than those treated with BSA. Moreover, rAN II treatment of HUVECs restored plasmin generation impaired by plasminogen activator inhibitor-1 or homocysteine pretreatment. In a rat carotid artery thrombus model, the patency of thrombosed carotid arteries was significantly enhanced by rAN II injection, in contrast to BSA injection, without systemic blood coagulation dysregulation. We found that rAN II enhanced plasmin generation on vascular endothelium in vitro and reduced thrombus formation in vivo, and concluded that enhancement of endothelial fibrinolytic activity by annexin II could modulate the hypercoagulable state of atherosclerosis. Further study of rAN II in vitro and in vivo may lead to the establishment of novel therapeutic approaches to thrombogenic vascular disease.

Key Words: annexin II • rat carotid artery • thrombus

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