Cohen-Hagai Keren, Rashid Gloria, Ohana Meital, Benchetrit Sydney, Zitman-Gal Tali
Renal Physiology Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel.
Medical Laboratories, Meir Medical Center, Kfar Saba, Israel.
Harefuah. 2017 Aug;156(8):486-489.
Diabetes mellitus (DM) is the leading cause of end-stage kidney disease. Inflammation, fibrosis, coagulability and oxidative stress exacerbate kidney disease. The glycoprotein, Von Willebrand Factor (VWF) has a crucial role in platelet thrombus formation. The enzyme ADAMTS13 is responsible for VWF cleavage. Both are important in the interface between diabetic nephropathy, hypercoagulability and atherosclerotic cardiovascular disease. Vitamin D inhibits endothelial proliferation, blunts angiogenesis and is a cardioprotective agent. This study evaluated the role of vitamin D on ADAMTS13 activity in human umbilical vein endothelial cells (HUVEC) exposed to a diabetic-like environment.
HUVEC were stimulated with 200µg/µl AGE-HSA, 250mg/dl glucose, and 10-10mol/l vitamin D for 24 hours. Western blot and ELISA techniques were used to determine ADAMTS13 protein expression and IL6 and IL8 protein secretion.
ADAMTS13 protein expression decreased and IL6 and IL8 protein secretion increased in HUVEC exposed to a diabetic-like environment. The addition of vitamin D significantly down-regulated IL6 and IL8 secretion and up-regulated ADAMST13 expression.
Decreased ADAMTS13 expression in HUVEC exposed to a diabetic-like environment may contribute to the pathogenesis of hypercoagulability observed in DM. Normalization of ADAMTS13 by vitamin D may contribute to improvement in hypercoagulability.
糖尿病（DM）是终末期肾病的主要病因。炎症、纤维化、凝血功能和氧化应激会加重肾脏疾病。糖蛋白血管性血友病因子（VWF）在血小板血栓形成中起关键作用。酶ADAMTS13负责VWF的裂解。二者在糖尿病肾病、高凝状态和动脉粥样硬化性心血管疾病之间的关联中都很重要。维生素D可抑制内皮细胞增殖、抑制血管生成，是一种心脏保护剂。本研究评估了维生素D对处于类糖尿病环境中的人脐静脉内皮细胞（HUVEC）中ADAMTS13活性的作用。
用200µg/µl 糖基化终末产物修饰的人血清白蛋白（AGE-HSA）、250mg/dl葡萄糖和10-10mol/l维生素D刺激HUVEC 24小时。采用蛋白质免疫印迹法和酶联免疫吸附测定（ELISA）技术测定ADAMTS13蛋白表达以及白细胞介素6（IL6）和白细胞介素8（IL8）蛋白分泌。
处于类糖尿病环境中的HUVEC中，ADAMTS13蛋白表达降低，IL6和IL8蛋白分泌增加。添加维生素D可显著下调IL6和IL8的分泌，并上调ADAMTS13的表达。
处于类糖尿病环境中的HUVEC中ADAMTS13表达降低可能导致糖尿病中观察到的高凝状态的发病机制。维生素D使ADAMTS13恢复正常可能有助于改善高凝状态。
