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(Circulation. 2003;108:2892.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Lung Endothelium Targeting for Pulmonary Embolism Thrombolysis

Bi-Sen Ding, BS; Ying-Jiang Zhou, BS; Xin-Yuan Chen, BS; Jing Zhang, PhD; Pei-Xiang Zhang, MS; Zi-Yong Sun, MS; Xiang-Yang Tan, MD; Jian-Ning Liu, PhD

From the Institute of Molecular Medicine and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China.

Correspondence to Jiang-Ning Liu or Xiang-Yang Tan, Institute of Molecular Medicine, Nanjing University, 22 Hankou Rd, Nanjing, 210093, China. E-mail jnliu{at}prodigy.net or xiangyangtan@yahoo.com.

Received August 25, 2003; de novo received September 25, 2003; accepted October 14, 2003.

Background— Pulmonary embolism occurs frequently in hospitalized patients. Thrombolytic therapy, currently used as the major treatment, has often been associated with severe bleeding complications and has thereby been life-threatening. We have developed a novel therapeutic method based on our newly created pulmonary endothelium-specific antibody.

Methods and Results— We isolated membrane proteins of rat pulmonary vascular luminal endothelium and obtained a monoclonal antibody, RE8F5, which antigen was uniquely expressed by the pulmonary capillary endothelium. In vivo biodistribution showed that RE8F5 and its urokinase conjugate were rapidly and specifically accumulated in lung. Urokinase and the conjugate were compared in rats with pulmonary, hepatic, and lower-limb embolus. In a pulmonary embolus model, the conjugate exhibited 12-fold enhanced thrombolytic potency over urokinase, whereas plasma fibrinogen and bleeding time were unaffected. In 2 other models, no significant thrombolysis was induced by the conjugate. In contrast, thrombolysis by urokinase was found to be comparable to the pulmonary embolus model. In addition, urokinase caused significant consumption of fibrinogen in all experiments.

Conclusions— These data show that urokinase equipped with lung endothelium-specific antibody is an ideal treatment for pulmonary embolism, with a high efficacy of thrombolysis and low risk of bleeding.

Key Words: pulmonary embolism • endothelium • thrombolysis • urokinase

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