title: Anti-thrombosis effect of LRRFIP1 shRNA lentivirus in a mouse model of deep vein thrombosis.
abstract: BACKGROUND
  Deep vein thrombosis (DVT) is one of the common complications of orthopedic surgery. Low molecular weight heparin (LMWH) is a usually used agent for DVT, but it would increase the risk of bleeding. LRRFIP1 has been shown to play an important role in the formation of thrombosis. Therefore, we investigated the effect of LRRFIP1 shRNA lentivirus on DVT in mice.
  
  
  METHODS
  Lentiviral Vectors carrying LRRFIP1 shRNA were constructed and transfected into cultured mouse bone marrow cells (BMCs). Male ICR mice were irradiated with a single dose of 9.5 Gy and then were injected with different agents through the tail vein. Stasis venous thrombosis was induced by inferior vena cava (IVC) ligation. Mice were sacrificed on the 1st, 3rd and 7th day post operation and the thrombi were removed, blotted the excess blood on it with filter paper and immediately weighed. P-selectin and d-Dimer were determined by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  LRRFIP1 shRNA significantly suppressed the expression of LRRFIP1 in the thrombi. In contrast, low molecular weight heparin (LMWH) and negative shRNA exhibited little effect on the expression of LRRFIP1. LRRFIP1 shRNA, LMWH and negative shRNA inhibited the thrombus formation in vivo significantly. The plasma P-selectin and d-Dimer levels were significantly increased after IVC ligation. LRRFIP1 shRNA significantly decreased the plasma P-selectin and d-Dimer levels. However, LMWH and negative shRNA showed little effects on the levels of plasma P-selectin and d-Dimer.
  
  
  CONCLUSIONS
  LRRFIP1 shRNA might represent a promising prevention strategy for DVT.
authors.affiliation: Department of orthopaedics, Institute of surgery research, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yin
authors.forename: Siyu
authors.initials: S
authors.lastname: Wu
authors.forename: Ziming
authors.initials: Z
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Quanyin
authors.initials: Q
authors.lastname: Du
authors.forename: Aimin
authors.initials: A
authors.lastname: Wang
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019007:P-Selectin / Q000097:blood / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*
chemical_list: D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D006495:Heparin, Low-Molecular-Weight; C558582:Lrrfip1 protein, mouse; D019007:P-Selectin; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C036309:fibrin fragment D
keywords: Anti-thrombosis; BMCs; DVT; Deep vein thrombosis; ELISA; GFP; IVC; LMWH; LRRFIP1; PE; THA; TKA; bone marrow cells; deep vein thrombosis; enzyme-linked immunosorbent assay; green fluorescent protein; inferior vena cava; leucine-rich repeat in Flightless-1 interaction protein 1; low molecular weight heparin; p-Selectin; pulmonary embolism; siRNA; small interfering RNA; total hip arthroplasty; total knee arthroplasty