Coagulation and fibrosis in chronic liver disease
Coagulation and fibrosis in chronic liver disease
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DOI：
10.1136/gut.2008.150748
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发表时间：
2008-12-01
期刊：
影响因子：
24.5
通讯作者：
Burroughs, A. K.
中科院分区：
文献类型：
--
作者：
Calvaruso, V.;Maimone, S.;Burroughs, A. K.
在肝组织修复机制中，肝星状细胞(HSCs)在损伤部位被招募，它们的变化反映了所有邻近细胞类型的旁分泌刺激，包括肝窦内皮细胞、Kupffer细胞、肝细胞、血小板和白细胞。凝血酶可将循环中的纤维蛋白原转化为纤维蛋白，促进血小板聚集，是一种强大的内皮细胞激活剂，对炎症细胞具有趋化作用，对成纤维细胞和血管平滑肌细胞具有有丝分裂原和趋化作用。凝血酶诱导的大部分细胞效应是通过广泛表达的G蛋白偶联受体家族介导的，该受体被称为蛋白酶激活受体(PARs)。所有已知的PAR家族成员都能刺激大鼠肝星状细胞系的细胞增殖/激活。凝血酶受体在肝脏中有结构性的表达，其表达随着肝脏疾病的严重程度和/或病程的延长而增加。在人体研究中，血栓危险因素被发现与纤维化的程度独立相关；与单纯丙型肝炎病毒携带者相比，与丙型肝炎病毒(HCV)相关的肝病严重程度相比，嗜血症患者的严重程度似乎更低。几项主要基于大鼠模型的研究表明，抗凝剂或抗血小板药物通过作用于HSC来防止肝坏死和纤维化。这些药物可能是慢性肝病患者的治疗剂，应该开始具体的研究。
In the hepatic tissue repair mechanism, hepatic stellate cells (HSCs) are recruited at the site of injury and their changes reflect paracrine stimulation by all neighbouring cell types, including sinusoidal endothelial cells, Kupffer cells, hepatocytes, platelets and leucocytes. Thrombin converts circulating fibrinogen to fibrin, promotes platelet aggregation, is a potent activator of endothelial cells, acts as a chemoattractant for inflammatory cells and is a mitogen and chemoattractant for fibroblasts and vascular smooth muscle cells. Most of the cellular effects elicited by thrombin are mediated via a family of widely expressed G-protein-coupled receptors termed protease activated receptors (PARs). All known members of the PAR family stimulate cell proliferation/activation in a rat HSC line. Thrombin receptors are constitutively expressed in the liver, and their expression increases in parallel with the severity and/or the duration of liver disease. In human studies, thrombotic risk factors were found to be independently associated with the extent of fibrosis; severity of hepatitis C virus (HCV)-associated liver disease appears to be less in patients with haemoihilia when compared with those with HCV alone. Several studies, based mostly on rat models, demonstrate that anticoagulants or antiplatelet agents prevent hepatic necrosis and fibrosis by acting on HSCs. These drugs could be therapeutic agents in patients with chronic liver disease and specific studies should be initiated.