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
目的探讨心绞痛患者血清白细胞介素-6受体(interleukin-6 receptor,IL-6R)及含N型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin and metalloprotease with thrombospondin type 1 motifs,ADAMTS-1)浓度与冠状动脉粥样硬...目的探讨心绞痛患者血清白细胞介素-6受体(interleukin-6 receptor,IL-6R)及含N型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin and metalloprotease with thrombospondin type 1 motifs,ADAMTS-1)浓度与冠状动脉粥样硬化病变程度及冠状动脉斑块稳定性的关系。方法本实验共选取患者223例:心绞痛患者167例,其中不稳定型心绞痛(unstable angina,UA)126例,稳定型心绞痛(stable angina,SA)41例;对照组56例。依据心绞痛患者冠状动脉造影结果进行Gensini评分,分为4个亚组(冠状动脉病变轻度、中度、重度、极重度亚组)。应用酶联免疫吸附试验(ELISA)法检测血清IL-6R、ADAMTS-1浓度,并测定血清总胆固醇、三酰甘油、低密度脂蛋白浓度。结果 UA组IL-6R与ADAMTS-1浓度较SA组明显增高,差异有统计学意义(P<0.05)。心绞痛不同冠状动脉病变程度4个亚组中血清IL-6R、ADAMTS-1浓度比较,差异无统计学意义(P>0.05)。结论外周血IL-6R与ADAMTS-1浓度与冠状动脉病变的严重程度无明显相关性,与冠状动脉粥样硬化斑块的稳定性相关。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
AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent livi...AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells,the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD,the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD,such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies,must be decided according to each case. CONCLUSION:The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.展开更多
含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-4(A disintegrin-like and metalloproteinase with thrombospondin type-1motifs-4,ADAMTS-4)属于ADAMTS金属蛋白酶家族中的一员,主要由巨噬细胞分泌,由无活性的酶原经过切割转化为具...含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-4(A disintegrin-like and metalloproteinase with thrombospondin type-1motifs-4,ADAMTS-4)属于ADAMTS金属蛋白酶家族中的一员,主要由巨噬细胞分泌,由无活性的酶原经过切割转化为具有活性的酶在细胞外发挥作用,ADATMS-4 mRNA表达受IFN-γ、TNF-α、IL-1β、IL-1、IL-6、TGF-β等多种因子的调控,参与了关节炎、骨关节病、癌症、心脏病等多种疾病的发生发展过程。作为一种新型炎症因子,ADAMTS-4在动脉粥样硬化的发展中起了重要作用,对动脉粥硬化斑块的不稳定性有影响,并且其在急性心肌梗死中的表达也有变化。因此,ADAMTS-4与冠状动脉粥样硬化性心脏病有着密切联系。文章就ADAMTS-4与冠心病的研究进展做一综述。展开更多
血栓性微血管病(Thrombotic microangiopathy,TMA)是一组以非免疫性血管内溶血和缺血性器官功能障碍为特征的疾病,包括原发性血栓性微血管病[如血栓性血小板减少性紫癜(Thrombotic thrombocytopenic purpura,TTP)等]和继发性血栓性微血...血栓性微血管病(Thrombotic microangiopathy,TMA)是一组以非免疫性血管内溶血和缺血性器官功能障碍为特征的疾病,包括原发性血栓性微血管病[如血栓性血小板减少性紫癜(Thrombotic thrombocytopenic purpura,TTP)等]和继发性血栓性微血管病[如弥散性血管内凝血(Disseminated intravascular coagulation,DIC)等]。目前血管性血友病因子裂解蛋白酶(A disintegrin and metalloprotease with a thrombospondin type 1 motif member 13,ADAMTS13)在TTP诊疗中的作用相对明确,但是否在其他血栓性微血管病的诊疗中存在同样重要的价值并不清楚,ADAMTS13作用于相关血栓性微血管病的具体机制较为复杂。ADAMTS13在DIC、系统性红斑狼疮肾炎以及严重肝损伤等相关血栓性微血管病中活性均有不同程度的降低,或许可作为该类疾病的辅助诊断指标。本文主要从ADAMTS13与血栓性微血管病的发病机制及其在相关血栓性微血管病诊疗中的应用价值进行综述。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.
文摘目的探讨心绞痛患者血清白细胞介素-6受体(interleukin-6 receptor,IL-6R)及含N型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1(a disintegrin and metalloprotease with thrombospondin type 1 motifs,ADAMTS-1)浓度与冠状动脉粥样硬化病变程度及冠状动脉斑块稳定性的关系。方法本实验共选取患者223例:心绞痛患者167例,其中不稳定型心绞痛(unstable angina,UA)126例,稳定型心绞痛(stable angina,SA)41例;对照组56例。依据心绞痛患者冠状动脉造影结果进行Gensini评分,分为4个亚组(冠状动脉病变轻度、中度、重度、极重度亚组)。应用酶联免疫吸附试验(ELISA)法检测血清IL-6R、ADAMTS-1浓度,并测定血清总胆固醇、三酰甘油、低密度脂蛋白浓度。结果 UA组IL-6R与ADAMTS-1浓度较SA组明显增高,差异有统计学意义(P<0.05)。心绞痛不同冠状动脉病变程度4个亚组中血清IL-6R、ADAMTS-1浓度比较,差异无统计学意义(P>0.05)。结论外周血IL-6R与ADAMTS-1浓度与冠状动脉病变的严重程度无明显相关性,与冠状动脉粥样硬化斑块的稳定性相关。
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。
基金Supported by the Grant from Uehara Memorial Foundation, No. 200940051, Tokyo, 171-0033, Japan
文摘AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells,the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD,the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD,such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies,must be decided according to each case. CONCLUSION:The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.
文摘含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-4(A disintegrin-like and metalloproteinase with thrombospondin type-1motifs-4,ADAMTS-4)属于ADAMTS金属蛋白酶家族中的一员,主要由巨噬细胞分泌,由无活性的酶原经过切割转化为具有活性的酶在细胞外发挥作用,ADATMS-4 mRNA表达受IFN-γ、TNF-α、IL-1β、IL-1、IL-6、TGF-β等多种因子的调控,参与了关节炎、骨关节病、癌症、心脏病等多种疾病的发生发展过程。作为一种新型炎症因子,ADAMTS-4在动脉粥样硬化的发展中起了重要作用,对动脉粥硬化斑块的不稳定性有影响,并且其在急性心肌梗死中的表达也有变化。因此,ADAMTS-4与冠状动脉粥样硬化性心脏病有着密切联系。文章就ADAMTS-4与冠心病的研究进展做一综述。
文摘血栓性微血管病(Thrombotic microangiopathy,TMA)是一组以非免疫性血管内溶血和缺血性器官功能障碍为特征的疾病,包括原发性血栓性微血管病[如血栓性血小板减少性紫癜(Thrombotic thrombocytopenic purpura,TTP)等]和继发性血栓性微血管病[如弥散性血管内凝血(Disseminated intravascular coagulation,DIC)等]。目前血管性血友病因子裂解蛋白酶(A disintegrin and metalloprotease with a thrombospondin type 1 motif member 13,ADAMTS13)在TTP诊疗中的作用相对明确,但是否在其他血栓性微血管病的诊疗中存在同样重要的价值并不清楚,ADAMTS13作用于相关血栓性微血管病的具体机制较为复杂。ADAMTS13在DIC、系统性红斑狼疮肾炎以及严重肝损伤等相关血栓性微血管病中活性均有不同程度的降低,或许可作为该类疾病的辅助诊断指标。本文主要从ADAMTS13与血栓性微血管病的发病机制及其在相关血栓性微血管病诊疗中的应用价值进行综述。
