Toshiaki Iba1, Koichiro Aihara2, Atushi Yamada2, Masataka Nagayama2, Yoko Tabe3, Akimichi Ohsaka4. 1. Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine. Electronic address: toshiiba@cf6.so-net.ne.jp. 2. Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine. 3. Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine. 4. Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University Graduate School of Medicine.
Abstract
INTRODUCTION: Thrombosis is a major complication in diabetes mellitus. Since Factor Xa inhibitors are not only inhibit the coagulation system but also attenuate the leukocyte-endothelial interaction in acute inflammation models, the purpose of this study is to confirm the similar effects of rivaroxaban in a mouse model of type 2 diabetes mellitus. MATERIALS AND METHODS: In the treatment groups, either 5 or 10mg/kg of rivaroxaban dissolved in DMSO was orally given to KK-A(y) mice for 7 weeks (n=6 in each group). KK-A(y) mice fed by chow containing DMSO without rivaroxaban for 7 weeks were served for the control group (n=6). Following clamping of the mesenteric vein for 20 minutes, intravital microscopic observation of the intestinal microcirculation and the measurement of bleeding time after the needle puncture were carried-out. In another series, the calculation for blood cell counts and the measurement of blood fluidity using micro channel array flow analyzer (MC-FAN) were performed. RESULTS: The initial event in the microvasculature is the leukocyte adhesion on endothelium. Then, the leukocytes make clusters and the platelets are involved in. These leukocyte-platelet conjugates aggregate and form thrombus. The leukocyte adherence and the microthrombus formation was significantly suppressed with the treatment of 10 mg/kg of rivaroxaban compared to the control group (P<0.05). While, the bleeding time was significantly extended with the treatment with 10mg/kg of rivaroxaban (P<0.01). The blood fluidity was maintained best with the treatment of 10 mg/kg rivaroxaban. CONCLUSIONS: Rivaroxaban attenuates the leukocyte-platelet-endothelial interaction, which leads to the attenuation of microthrombus formation in a mouse model of diabetes mellitus.
INTRODUCTION:Thrombosis is a major complication in diabetes mellitus. Since Factor Xa inhibitors are not only inhibit the coagulation system but also attenuate the leukocyte-endothelial interaction in acute inflammation models, the purpose of this study is to confirm the similar effects of rivaroxaban in a mouse model of type 2 diabetes mellitus. MATERIALS AND METHODS: In the treatment groups, either 5 or 10mg/kg of rivaroxaban dissolved in DMSO was orally given to KK-A(y) mice for 7 weeks (n=6 in each group). KK-A(y) mice fed by chow containing DMSO without rivaroxaban for 7 weeks were served for the control group (n=6). Following clamping of the mesenteric vein for 20 minutes, intravital microscopic observation of the intestinal microcirculation and the measurement of bleeding time after the needle puncture were carried-out. In another series, the calculation for blood cell counts and the measurement of blood fluidity using micro channel array flow analyzer (MC-FAN) were performed. RESULTS: The initial event in the microvasculature is the leukocyte adhesion on endothelium. Then, the leukocytes make clusters and the platelets are involved in. These leukocyte-platelet conjugates aggregate and form thrombus. The leukocyte adherence and the microthrombus formation was significantly suppressed with the treatment of 10 mg/kg of rivaroxaban compared to the control group (P<0.05). While, the bleeding time was significantly extended with the treatment with 10mg/kg of rivaroxaban (P<0.01). The blood fluidity was maintained best with the treatment of 10 mg/kg rivaroxaban. CONCLUSIONS:Rivaroxaban attenuates the leukocyte-platelet-endothelial interaction, which leads to the attenuation of microthrombus formation in a mouse model of diabetes mellitus.
Authors: Fernando Góngora-Rivera; Héctor R Martínez; Leonel Cantu-Martinez; Carlos R Camara-Lemarroy; Talía Moreno-Andrade Journal: J Vasc Interv Neurol Date: 2018-11
Authors: T G Mastenbroek; M F A Karel; M Nagy; W Chayoua; E I J Korsten; D M Coenen; J Debets; J Konings; A E Brouns; P J A Leenders; H van Essen; R van Oerle; S Heitmeier; H M Spronk; M J E Kuijpers; J M E M Cosemans Journal: Sci Rep Date: 2020-11-09 Impact factor: 4.379