Role of osteopontin in cardiac fibrosis and remodeling in angiotensin II - Induced cardiac hypertrophy
Role of osteopontin in cardiac fibrosis and remodeling in angiotensin II - Induced cardiac hypertrophy
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DOI：
10.1161/01.hyp.0000128621.68160.dd
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发表时间：
2004-06-01
期刊：
影响因子：
8.3
通讯作者：
Uede, T
中科院分区：
文献类型：
--
作者：
Matsui, Y;Jia, N;Uede, T
骨桥蛋白（OPN）在一些心脏纤维化和重构的实验模型中上调。然而，其直接影响尚不清楚。我们检验了OPN对心脏纤维化和重构的发展很重要的假设。此外，我们研究了新型醛固酮受体拮抗剂eplerenone （Ep）的抑制作用是否通过抑制OPN对心脏纤维化和重构的表达来介导。野生型（WT）和opn缺陷小鼠用血管紧张素II （Ang II）治疗4周。将接受angii治疗的WT小鼠分为两组：对照组和Ep治疗组。angii治疗显著升高WT小鼠血压，并引起心肌肥大和纤维化。Ep治疗和OPN缺乏可降低angii诱导的血压升高，改善心肌纤维化的发展，而Ep治疗可消除心肌肥厚的发展。最令人信服的是，在angii治疗的opn缺陷小鼠中，心脏纤维化的减少导致心脏收缩功能受损和随后的左心室扩张。这些结果表明，OPN在Ang ii诱导的心脏纤维化和重构的发展中起关键作用。此外，Ep对心肌纤维化而非心肌肥厚的预防作用可能部分通过抑制OPN表达介导。
Osteopontin (OPN) is upregulated in several experimental models of cardiac fibrosis and remodeling. However, its direct effects remain unclear. We examined the hypothesis that OPN is important for the development of cardiac fibrosis and remodeling. Moreover, we examined whether the inhibitory effect of eplerenone (Ep), a novel aldosterone receptor antagonist, was mediated through the inhibition of OPN expression against cardiac fibrosis and remodeling. Wild-type (WT) and OPN-deficient mice were treated with angiotensin II (Ang II) for 4 weeks. WT mice receiving Ang II were divided into 2 groups: a control group and an Ep treatment group. Ang II treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in WT mice. Ep treatment and OPN deficiency could reduce the Ang II-induced elevation of blood pressure and ameliorate the development of cardiac fibrosis, whereas Ep-only treatment abolished the development of cardiac hypertrophy. Most compelling, the reduction of cardiac fibrosis led to an impairment of cardiac systolic function and subsequent left ventricular dilatation in Ang II-treated OPN-deficient mice. These results suggest that OPN has a pivotal role in the development of Ang II-induced cardiac fibrosis and remodeling. Moreover, the effect of Ep on the prevention of cardiac fibrosis, but not cardiac hypertrophy, might be partially mediated through the inhibition of OPN expression.