Therapy Promotes Venous Thromboembolism Through The...

Antiangiogeneic therapy promotes venous thromboembolism through the induction of PAI-1 in a mouse xenograft model of human lung carcinoma Ni Chen1*, Meiping Ren1*, Rong Li1, Xin Deng1, Yongjie Li1, Kai Yan1, Lamei Xiao1 , Yan Yang1, Liqun Wang 1, Mao Luo 1, William P. Fay 2, Jianbo Wu1,2 1Drug Discovery Research Center, Luzhou, Sichuan, People s Republic of China; 2Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO, USA Corresponding author: Jianbo Wu, Division of Cardiovascular Medicine, University of Missouri, 5 Hospital Drive, CE344–DC095.00, Columbia, Missouri 65212. Email: wuji@missouri.edu, Phone: 573-884-4040, Fax: (573) 884-7743. * These authors contributed equally to this work. Key Points †¢ Bevacizumab promotes VTE through the induction of PAI-1 in a mouse xenograft model of human lung carcinoma †¢ Treatment with a PAI-1 inhibitor reduces bevacizumab-induced VTE. Abstract Thromboembolism is a major source of morbidity and mortality in patients with cancer. An increased incidence of venous thromboembolism (VTE) is associated with anti-vascular endothelial growth factor (VEGF) treatment in cancer. However, the mechanism of VTE initiation remains elusive. In this study, we examined the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A, on either an inferior vena cava stenosis or saphenous vein model in a xenograft mouse model. We found that treatment with bevacizumab accelerated