Angiotensin II induces contraction and proliferation of human hepatic stellate cells
Angiotensin II induces contraction and proliferation of human hepatic stellate cells
复制标题
DOI：
10.1016/s0016-5085(00)70368-4
复制
发表时间：
2000-06-01
期刊：
影响因子：
29.4
通讯作者：
Rodés, J
中科院分区：
文献类型：
--
作者：
Bataller, R;Ginès, P;Rodés, J
背景和目标：血管紧张素II（ANGII）是一种强有力的血管收缩因子，其循环水平在慢性肝病中经常升高。在这些条件下，肝星状细胞（HSC）增殖并获得收缩特性。本研究调查了ANGII受体的存在和ANGII在培养物中活化的人HSC中的作用。研究方法：通过结合研究评估ANGII受体的存在。还评估了ANGII对细胞内钙浓度（[Ca-2+]（i））、细胞收缩和细胞增殖的影响。结果：结合研究显示存在AT 1亚型的ANGII受体。ANGII引起[Ca 2 +]（i）和细胞收缩的显著剂量依赖性增加。此外，ANGII刺激DNA合成并增加细胞数量。所有这些作用都被氯沙坦完全阻断，并被一氧化氮供体或前列腺素E-2降低。ANGII的作用在静止细胞（培养2天）中几乎检测不到，表明HSC的表型转化与ANGII作用的显著增加相关。结论：ANGII通过AT 1受体作用于人活化的HSC，诱导收缩并促有丝分裂。这些结果表明，活化的HSC是ANGII在肝内循环中血管收缩作用的靶点。
Background & Aims: Circulating levels of angiotensin II (ANGII), a powerful vasoconstrictor factor, are frequently increased in chronic liver diseases. In these conditions, hepatic stellate cells (HSCs) proliferate and acquire contractile properties. This study investigated the presence of receptors for ANGII and the effects of ANGII in human HSCs activated in culture. Methods: The presence of ANGII receptors was assessed by binding studies, The effects of ANGII on intracellular calcium concentration ([Ca-2+](i)), cell contraction, and cell proliferation were also assessed. Results: Binding studies showed the presence of ANGII receptors of the AT1 subtype. ANGII elicited a marked dose-dependent increase in [Ca2+](i) and cell contraction. Moreover, ANGII stimulated DNA synthesis and increased cell number. All these effects were totally blocked by losartan and reduced by nitric oxide donors or prostaglandin E-2. The effects of ANGII were barely detectable in quiescent cells (2 days in culture), suggesting that phenotypic transformation of HSCs is associated with a marked increase in the effect of ANGII. Conclusions: ANGII induces contraction and is mitogenic for human-activated HSCs by acting through AT1 receptors, These results suggest that activated HSCs are targets of the vasoconstrictor action of ANGII in the intrahepatic circulation.