Disruption of mindin exacerbates cardiac hypertrophy and fibrosis.
Disruption of mindin exacerbates cardiac hypertrophy and fibrosis.
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Mindin 的破坏会加剧心脏肥大和纤维化
DOI：
10.1007/s00109-012-0883-2
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发表时间：
2012-08
影响因子：
4.7
通讯作者：
Li, Hongliang
中科院分区：
文献类型：
--
作者：
Bian, Zhou-Yan;Wei, Xiang;Deng, Shan;Tang, Qi-Zhu;Feng, Jinghua;Zhang, Yan;Liu, Chen;Jiang, Ding-Sheng;Yan, Ling;Zhang, Lian-Feng;Chen, Manyin;Fassett, John;Chen, Yingjie;He, You-Wen;Yang, Qinglin;Liu, Peter P.;Li, Hongliang
心脏肥大是心肌对增加的工作负荷的反应，其特征是心肌质量增加和细胞外基质（ECM）积聚。作为ECM蛋白、整合素配体和血管生成抑制剂，它们都是心脏肥大的关键参与者，mindin是用于治疗或预防心脏肥大和心力衰竭的治疗性干预的有吸引力的靶标。在这项研究中，我们使用同窝Mindin敲除（Mindin-/-）和野生型（WT）小鼠研究了mindin在心脏肥大中的作用。在Mindin −/−和WT小鼠中，通过主动脉缩窄（AB）或血管紧张素II（Ang II）输注诱导心脏肥大。心脏肥大的程度通过超声心动图和心脏样本的病理学和分子分析来定量。Mindin−/−小鼠对AB或Ang II刺激的心脏肥大和纤维化反应比野生型更敏感。在Mindin −/−小鼠的心脏收缩期和舒张期，心脏功能也因肥大刺激而明显恶化。蛋白质印迹分析进一步表明，在Mindin −/−小鼠中，响应肥大刺激的AKT/糖原合成酶激酶3β（GSK 3 β）信号传导的激活显著增加。此外，用药理学AKT抑制剂阻断AKT/GSK 3 β信号传导可逆转Mindin −/−小鼠的心脏异常。我们的数据表明，mindin作为一种内在的心脏保护因子，通过阻断AKT/GSK 3 β信号传导来防止适应不良重构和向心力衰竭的转变。
Cardiac hypertrophy is a response of the myocardium to increased workload and is characterised by an increase of myocardial mass and an accumulation of extracellular matrix (ECM). As an ECM protein, an integrin ligand, and an angiogenesis inhibitor, all of which are key players in cardiac hypertrophy, mindin is an attractive target for therapeutic intervention to treat or prevent cardiac hypertrophy and heart failure. In this study, we investigated the role of mindin in cardiac hypertrophy using littermateMindinknockout (Mindin−/−) and wild-type (WT) mice. Cardiac hypertrophy was induced by aortic banding (AB) or angiotensin II (Ang II) infusion inMindin−/−and WT mice. The extent of cardiac hypertrophy was quantitated by echocardiography and by pathological and molecular analyses of heart samples.Mindin−/−mice were more susceptible to cardiac hypertrophy and fibrosis in response to AB or Ang II stimulation than wild type. Cardiac function was also markedly exacerbated during both systole and diastole inMindin−/−mice in response to hypertrophic stimuli. Western blot assays further showed that the activation of AKT/glycogen synthase kinase 3β (GSK3β) signalling in response to hypertrophic stimuli was significantly increased inMindin−/−mice. Moreover, blocking AKT/GSK3β signalling with a pharmacological AKT inhibitor reversed cardiac abnormalities inMindin−/−mice. Our data show that mindin, as an intrinsic cardioprotective factor, prevents maladaptive remodelling and the transition to heart failure by blocking AKT/GSK3β signalling.
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影响因子：
5.6
作者：
Terai, Y;Abe, M;Sato, Y
通讯作者：
Sato, Y
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5
作者：
Taniyama, Yoshiaki;Ito, Masahiro;Shiojima, Ichiro
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Shiojima, Ichiro
影响因子：
20.1
作者：
Shai, SY;Harpf, AE;Ross, RS
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Ross, RS
影响因子：
5.3
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Cai J;Yi FF;Bian ZY;Shen DF;Yang L;Yan L;Tang QZ;Yang XC;Li H
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Li H
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4.8
作者：
Matsui, T;Li, L;Rosenzweig, A
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Rosenzweig, A