title: Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model.
abstract: : L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis.
authors.affiliation: aDepartment of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University bLaboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University cJiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University dDepartment of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, PR China *Bingyang Dai and Lan Li contributed equally to the writing of this article.
authors.forename: Bingyang
authors.initials: B
authors.lastname: Dai
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Song
authors.forename: Dongyang
authors.initials: D
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yan
authors.forename: Huajian
authors.initials: H
authors.lastname: Teng
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D019007:P-Selectin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014684:Venae Cavae / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D019007:P-Selectin; D001120:Arginine