Aldosterone increases plasminogen activator inhibitor-1 synthesis in rat cardiomyocytes
Aldosterone increases plasminogen activator inhibitor-1 synthesis in rat cardiomyocytes
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DOI：
10.1016/j.mce.2005.03.016
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发表时间：
2005-07-15
影响因子：
4.1
通讯作者：
Pratt, JH
中科院分区：
文献类型：
--
作者：
Chun, TY;Pratt, JH
纤溶酶原激活物抑制剂-1（PAT-1）是一种抗血栓溶解因子，也可促进组织纤维化。在某些情况下，暴露于醛固酮可导致心脏纤维化的一个未知的机制。在目前的研究中，我们验证了派-1是醛固酮纤维化作用的介质的假设。醛固酮增加派-1 mRNA和蛋白在H9 c2大鼠心肌细胞系中的水平，可被盐皮质激素受体（MR）拮抗剂螺内酯阻断的反应。共聚焦显微镜证实了醛固酮增加派-1表达的作用，并被螺内酯逆转。醛固酮还增加派-1在新生大鼠心肌细胞的表达，这再次被螺内酯阻断。在新生心肌细胞（但不是H9 c2细胞）中，抗转化生长因子β 1抗体抑制派-1对醛固酮的反应。总之，醛固酮直接增加派-1的表达在两种不同的心肌细胞类型，依赖于MR的效果。在新生儿细胞中，似乎是一个需要转化生长因子β 1。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Plasminogen activator inhibitor-1 (PAT-1) is an anti-thrombolytic factor that also promotes tissue fibrosis. Under certain conditions, exposure to aldosterone can result in cardiac fibrosis by an unknown mechanism. In the current study, we tested the hypothesis that PAI-1 is a mediator of aldosterone's fibrotic effects. Aldosterone increased levels of PAI-1 mRNA and protein in the H9c2 rat cardiac cell line, responses that could be blocked by the mineralocorticoid receptor (MR) antagonist spironolactone. Confocal microscopy confirmed an effect of aldosterone to increase PAI-1 expression with reversal by spironolactone. Aldosterone also increased PAI-1 expression in neonatal rat cardiomyocytes, which was again blocked by spironolactone. In the neonatal cardiomyocytes (but not the H9c2 cells), anti-transforming growth factor-beta 1 antibody inhibited the PAI-1 response to aldosterone. In summary, aldosterone directly increased PAI-1 expression in two different cardiac muscle cell types, an effect that was dependent on MR. In the neonatal cells, there appeared to be a requirement for transforming growth factor-beta 1. (c) 2005 Elsevier Ireland Ltd. All rights reserved.