Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits.
Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits.
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DOI：
10.1371/journal.pone.0177660
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Roth DM
中科院分区：
文献类型：
--
作者：
Ichikawa Y;Zemljic-Harpf AE;Zhang Z;McKirnan MD;Manso AM;Ross RS;Hammond HK;Patel HH;Roth DM
蒽环类药物是一种化疗药物，已知以剂量依赖的方式诱导心力衰竭。蒽环类药物心脏毒性的机制是一个相关的研究领域。小窝蛋白结合、组织和调节细胞膜内的受体和信号分子。Caveolin-3 （Cav-3）、整合素及相关的膜修复蛋白可作为心脏保护蛋白。这些蛋白在蒽环类药物引起的心力衰竭中的表达尚未得到评估。我们检验了柔红霉素改变心脏保护蛋白表达的假设。兔每周给予柔红霉素（3mg /kg，静脉注射），连续3周或9周。柔红霉素使用9周而不是3周导致左心室功能进行性降低。在柔红霉素治疗三周后，心脏中Cav-3的表达没有变化，而在治疗九周后，与对照组心脏相比，Cav-3的表达有所增加。电镜观察显示，给药9周后，心肌小泡增多，线粒体数量和大小减小。激活的β -1 （β1）整合素和膜修复蛋白MG53在柔红霉素治疗9周后与对照组相比有所增加，在3周时间点没有变化。这些结果提示Cav3、整合素和膜修复在柔红霉素诱导的心力衰竭中具有潜在的病理生理作用。
Anthracyclines are chemotherapeutic drugs known to induce heart failure in a dose-dependent manner. Mechanisms involved in anthracycline cardiotoxicity are an area of relevant investigation. Caveolins bind, organize and regulate receptors and signaling molecules within cell membranes. Caveolin-3 (Cav-3), integrins and related membrane repair proteins can function as cardioprotective proteins. Expression of these proteins in anthracycline-induced heart failure has not been evaluated. We tested the hypothesis that daunorubicin alters cardioprotective protein expression in the heart. Rabbits were administered daunorubicin (3 mg/kg, IV) weekly, for three weeks or nine weeks. Nine weeks but not three weeks of daunorubicin resulted in progressive reduced left ventricular function. Cav-3 expression in the heart was unchanged at three weeks of daunorubicin and increased in nine week treated rabbits when compared to control hearts. Electron microscopy showed caveolae in the heart were increased and mitochondrial number and size were decreased after nine weeks of daunorubicin. Activated beta-1 (β1) integrin and the membrane repair protein MG53 were increased after nine weeks of daunorubicin vs. controls with no change at the three week time point. The results suggest a potential pathophysiological role for Cav3, integrins and membrane repair in daunorubicin-induced heart failure.