Controlling cardiomyocyte length: the role of renin and PPAR-γ
Controlling cardiomyocyte length: the role of renin and PPAR-γ
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DOI：
10.1093/cvr/cvq313
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发表时间：
2011-02-01
影响因子：
10.8
通讯作者：
Schlueter, Klaus-Dieter
中科院分区：
文献类型：
--
作者：
Hinrichs, Soehnke;Heger, Jacqueline;Schlueter, Klaus-Dieter
目的：研究肾素和过氧化物酶体增殖物激活受体（PPAR-gamma）与心肌细胞的相互作用，影响心肌细胞蛋白质合成。我们研究了它们的影响和相互作用的心肌细胞的大小。方法和结果的影响，肾素和PPAR-gamma激活培养的成年大鼠心室心肌细胞，转基因小鼠与心肌细胞限制性敲除的PPAR-gamma，和转基因大鼠过度表达肾素，TGR（mRen 2）27。在给予因子后24 h分析心肌细胞的长度和宽度。肾素对心肌细胞的长度产生了意想不到的影响，这种影响被甘露糖-6-磷酸和莫能菌素抑制，但不被葡萄糖-6-磷酸给药所抑制。内皮素-1作为一个经典的促肥大激动剂增加细胞宽度，但不增加细胞长度。肾素引起p38和p42/44丝裂原活化蛋白（MAP）激酶的激活。后者的激活受损的甘露糖-6-磷酸。抑制p42/44而不是p38 MAP激酶激活减弱了肾素对细胞长度的影响。相反，激活的PPAR-gamma减少细胞长度。用吡格列酮（一种PPAR-gamma激动剂）喂养野生型小鼠，细胞长度减少。从PPAR-gamma基因敲除小鼠中分离的心肌细胞更长，并且其长度不受吡格列酮的影响。从TGR（mRen 2）27大鼠分离的心肌细胞比非转基因同窝出生的大鼠的心肌细胞长。通过给这些小鼠喂吡格列酮，细胞长度减少。结论吡格列酮对心肌细胞长度的影响与心肌特异性6-磷酸甘露糖/胰岛素样生长因子II受体和PPAR-gamma的激活有关。这种类型的细胞大小修饰不同于任何其他已知的促肥大激动剂。
Aims Renin and peroxisome proliferator-activated receptor (PPAR-gamma) interact directly with cardiomyocytes and influence protein synthesis. We investigated their effects and interaction on the size of cardiomyocytes.Methods and results Effects of renin and PPAR-gamma activation were studied in cultured adult rat ventricular cardiomyocytes, transgenic mice with a cardiomyocyte-restricted knockout of PPAR-gamma, and transgenic rats overexpressing renin, TGR(mRen2)27. The length and width of cardiomyocytes were analysed 24 h after administration of factors. Renin caused an unexpected effect on the length of cardiomyocytes that was inhibited by mannose-6-phosphate and monensin, but not by administration of glucose-6-phosphate. Endothelin-1 used as a classical pro-hypertrophic agonist increased cell width but not cell length. Renin caused an activation of p38 and p42/44 mitogen-activated protein (MAP) kinases. The latter activation was impaired by mannose-6-phosphate. Inhibition of p42/44 but not of p38 MAP kinase activation attenuated the effect of renin on cell length. In contrast, activation of PPAR-gamma reduced cell length. Feeding wild-type mice with pioglitazone, a PPAR-gamma agonist, reduced cell length. Cardiomyocytes isolated from PPAR-gamma knockout mice were longer, and their length was not affected by pioglitazone. Cardiomyocytes isolated from TGR(mRen2) 27 rats were longer than those of non-transgenic littermates. Cell length was reduced by feeding these mice with pioglitazone. Pioglitazone affected cell length independent of blood pressure.Conclusion The length of cardiomyocytes is controlled by the activation of cardiac-specific mannose-6-phosphate/insulin-like growth factor II receptors and activation of PPAR-gamma. This type of cell size modification differs from that of any other known pro-hypertrophic agonists.