A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) specifically cleaves unusually-large von Willebrand factor(VWF) multimers under high shear stress,and down-regulates VWF function...A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) specifically cleaves unusually-large von Willebrand factor(VWF) multimers under high shear stress,and down-regulates VWF function to form platelet thrombi.Deficiency of plasma ADAMTS13 activity induces a life-threatening systemic disease,termed thrombotic microangiopathy(TMA) including thrombotic thrombocytopenic purpura(TTP).Children with advanced biliary cirrhosis due to congenital biliary atresia sometimes showed pathological features of TMA,with a concomitant decrease of plasma ADAMTS13 activity.Disappearance of their clinical findings of TTP after successful liver transplantation suggested that the liver is a major organ producing plasma ADAMTS13.In situ hybridization analysis showed that ADAMTS13 was produced by hepatic stellate cells.Subsequently,it was found that ADADTS13 was not merely responsible to development of TMA and TTP,but also related to some kinds of liver dysfunction after liver transplantation.Ischemia-reperfusion injury and acute rejection in liver transplant recipients were often associated with marked decrease of ADAMTS13 and concomitant formation of unusually large VWF multimers without findings of TMA/TTP.The similar phenomenon was observed also in patients who underwent hepatectomy for liver tumors.Imbalance between ADAMTS13 and VWF in the hepatic sinusoid might cause liver damage due to microcirculatory disturbance.It can be called as "local TTP like mechanism" which plays a crucial role in liver dysfunction after liver transplantation and surgery.展开更多
目的:通过系统评价与Meta分析探索Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶7(ADAMTS7)基因rs3825807位点单核苷酸的多态性与冠心病发病风险的关联。方法:计算机检索PubMed, Web of Science, Cochrane Library,中国知网,万方,维普...目的:通过系统评价与Meta分析探索Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶7(ADAMTS7)基因rs3825807位点单核苷酸的多态性与冠心病发病风险的关联。方法:计算机检索PubMed, Web of Science, Cochrane Library,中国知网,万方,维普和中国生物医学数据库,以获取ADAMTS7基因rs3825807多态性与冠心病易感性的原始研究。检索时限均为建库至2019年12月6日。由两位研究者独立筛选文献、提取数据并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果:共纳入6个病例-对照研究,观察组包括4 989例病例,对照组包含5 471例。Meta分析结果显示,患者ADAMTS7基因rs3825807多态性与冠心病的发病风险增加有相关性(AA vs, GG:OR=21.07,95%CI:1.61~275.95,P=0.02;AG vs. GG:OR=6.80,95%CI:0.77~60.11,P=0.08;AA+AG vs. GG:OR=13.19,95%CI:1.09~158.97,P=0.04;AA vs. AG+GG:OR=2.39,95%CI:1.44~3.96,P=0.0007;A vs. G:OR=23.44,95%CI:8.19~67.10,P<0.00001)。结论:患者ADAMTS7基因rs3825807多态性是冠心病的发病风险因素之一。受纳入研究数量和质量限制,本研究需更多的高质量临床研究予以验证。展开更多
目的:检测大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期海马组织中含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin-like and metalloproteinase with thrombospondin type l motifs,ADAMTS-1)在基底动脉...目的:检测大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期海马组织中含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin-like and metalloproteinase with thrombospondin type l motifs,ADAMTS-1)在基底动脉中的表达,分析其与大鼠SAH后急性脑血管痉挛(cerebral vasospasm,CVS)的相关性,探讨其在SAH后早期脑损伤(earlybrain injury,EBI)中的作用。方法:健康雄性成年SD大鼠108只,体质量250～300g,随机分为SAH组(n=90)和假手术组(sham组,n=18)。SAH组取大鼠自体动脉血,用视交叉池注血法建立大鼠SAH模型(sham组注入等量0.9%氯化钠液)。将SAH组随机分为6h、12h、24h、48h、72h5个亚组,每个亚组18只,分别在相应时间点处死。用蛋白质印迹(Western-blot)方法及实时荧光定量逆转录-聚合酶链反应(RT-PCR)法检测SAH各亚组及sham组基底动脉ADAMTS-1的表达,同时用HE染色法对基底动脉进行形态学观察。探讨ADAMTS-1与实验性大鼠SAH后急性CVS的相关性。结果:与sham组相比,SAH 6h亚组基底动脉ADAMTS-1表达无显著差异;12h亚组基底动脉ADAMTS-1蛋白表达显著增高,24h亚组最高,48h亚组、72h亚组逐渐下降,但仍维持在较高水平。与sham组相比,SAH 6h亚组大鼠基底动脉变化不明显;12h亚组大鼠基底动脉管腔缩小,管壁增厚;24h亚组基底动脉痉挛最为明显;48h亚组基底动脉痉挛较24h亚组减轻;与24h亚组、48h亚组相比,72h亚组基底动脉管腔直径更大、管壁厚度更薄。ADAMTS-1蛋白表达与SAH后急性CVS呈正相关(r=0.916,P=0.003)。结论:大鼠SAH后早期基底动脉ADAMTS-1表达与急性CVS正相关,提示ADAMTS-1可能参与大鼠SAH后EBI的病理过程。展开更多
文摘A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) specifically cleaves unusually-large von Willebrand factor(VWF) multimers under high shear stress,and down-regulates VWF function to form platelet thrombi.Deficiency of plasma ADAMTS13 activity induces a life-threatening systemic disease,termed thrombotic microangiopathy(TMA) including thrombotic thrombocytopenic purpura(TTP).Children with advanced biliary cirrhosis due to congenital biliary atresia sometimes showed pathological features of TMA,with a concomitant decrease of plasma ADAMTS13 activity.Disappearance of their clinical findings of TTP after successful liver transplantation suggested that the liver is a major organ producing plasma ADAMTS13.In situ hybridization analysis showed that ADAMTS13 was produced by hepatic stellate cells.Subsequently,it was found that ADADTS13 was not merely responsible to development of TMA and TTP,but also related to some kinds of liver dysfunction after liver transplantation.Ischemia-reperfusion injury and acute rejection in liver transplant recipients were often associated with marked decrease of ADAMTS13 and concomitant formation of unusually large VWF multimers without findings of TMA/TTP.The similar phenomenon was observed also in patients who underwent hepatectomy for liver tumors.Imbalance between ADAMTS13 and VWF in the hepatic sinusoid might cause liver damage due to microcirculatory disturbance.It can be called as "local TTP like mechanism" which plays a crucial role in liver dysfunction after liver transplantation and surgery.
文摘椎间盘退变(intervertebral disc degeneration,IVDD)可导致多种脊柱相关疾病的发生。细胞外基质(extracellular matrix,ECM)的降解被认为是IVDD的主要病理过程。基质金属蛋白酶(matrix metalloproteinases,MMPs)及含凝血酶敏感蛋白模体的解整合素样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motif,ADAMTSs)是参与ECM降解的主要蛋白酶类。本文总结在IVDD中MMPs、ADAMTSs及金属蛋白酶组织抑制剂(tissue inhibitors of metalloproteinases,TIMPs)的基因表达调控相关研究。研究发现人IVDD中MMP-1、2、3、7、8、10、13,ADAMTS-1、4、5出现表达上调,TIMP-3下调、TIMP-1上调。MMPs、ADAMTSs的表达受多因素共同调节,包括机械应力、炎症、氧化应激等,部分参与P38途径。遗传因素也在MMP-1、2、3、9的表达中起重要作用。MMPs、ADAMTSs蛋白表达及酶活性的上调导致ECM降解,进一步导致IVDD的发展。未来的治疗将靶向于导致ECM病理降解的特定MMPs及ADAMTSs。
文摘目的:通过系统评价与Meta分析探索Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶7(ADAMTS7)基因rs3825807位点单核苷酸的多态性与冠心病发病风险的关联。方法:计算机检索PubMed, Web of Science, Cochrane Library,中国知网,万方,维普和中国生物医学数据库,以获取ADAMTS7基因rs3825807多态性与冠心病易感性的原始研究。检索时限均为建库至2019年12月6日。由两位研究者独立筛选文献、提取数据并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果:共纳入6个病例-对照研究,观察组包括4 989例病例,对照组包含5 471例。Meta分析结果显示,患者ADAMTS7基因rs3825807多态性与冠心病的发病风险增加有相关性(AA vs, GG:OR=21.07,95%CI:1.61~275.95,P=0.02;AG vs. GG:OR=6.80,95%CI:0.77~60.11,P=0.08;AA+AG vs. GG:OR=13.19,95%CI:1.09~158.97,P=0.04;AA vs. AG+GG:OR=2.39,95%CI:1.44~3.96,P=0.0007;A vs. G:OR=23.44,95%CI:8.19~67.10,P<0.00001)。结论:患者ADAMTS7基因rs3825807多态性是冠心病的发病风险因素之一。受纳入研究数量和质量限制,本研究需更多的高质量临床研究予以验证。
文摘目的:检测大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期海马组织中含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin-like and metalloproteinase with thrombospondin type l motifs,ADAMTS-1)在基底动脉中的表达,分析其与大鼠SAH后急性脑血管痉挛(cerebral vasospasm,CVS)的相关性,探讨其在SAH后早期脑损伤(earlybrain injury,EBI)中的作用。方法:健康雄性成年SD大鼠108只,体质量250～300g,随机分为SAH组(n=90)和假手术组(sham组,n=18)。SAH组取大鼠自体动脉血,用视交叉池注血法建立大鼠SAH模型(sham组注入等量0.9%氯化钠液)。将SAH组随机分为6h、12h、24h、48h、72h5个亚组,每个亚组18只,分别在相应时间点处死。用蛋白质印迹(Western-blot)方法及实时荧光定量逆转录-聚合酶链反应(RT-PCR)法检测SAH各亚组及sham组基底动脉ADAMTS-1的表达,同时用HE染色法对基底动脉进行形态学观察。探讨ADAMTS-1与实验性大鼠SAH后急性CVS的相关性。结果:与sham组相比,SAH 6h亚组基底动脉ADAMTS-1表达无显著差异;12h亚组基底动脉ADAMTS-1蛋白表达显著增高,24h亚组最高,48h亚组、72h亚组逐渐下降,但仍维持在较高水平。与sham组相比,SAH 6h亚组大鼠基底动脉变化不明显;12h亚组大鼠基底动脉管腔缩小,管壁增厚;24h亚组基底动脉痉挛最为明显;48h亚组基底动脉痉挛较24h亚组减轻;与24h亚组、48h亚组相比,72h亚组基底动脉管腔直径更大、管壁厚度更薄。ADAMTS-1蛋白表达与SAH后急性CVS呈正相关(r=0.916,P=0.003)。结论:大鼠SAH后早期基底动脉ADAMTS-1表达与急性CVS正相关,提示ADAMTS-1可能参与大鼠SAH后EBI的病理过程。
