Early dystrophin loss is coincident with the transition of compensated cardiac hypertrophy to heart failure.
Early dystrophin loss is coincident with the transition of compensated cardiac hypertrophy to heart failure.
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DOI：
10.1371/journal.pone.0189469
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Prado CM
中科院分区：
文献类型：
--
作者：
Prado FP;Dos Santos DO;Blefari V;Silva CA;Machado J;Kettelhut IDC;Ramos SG;Baruffi MD;Salgado HC;Prado CM
高血压导致心脏肥大，这是心力衰竭（HF）最重要的危险因素之一。尽管心脏肥大作为HF发展的危险因素的重要性，但并非所有肥大的心脏最终都会衰竭。细胞骨架和肌膜相关蛋白的改变被认为是HF期间心脏重塑的标志。肌营养不良蛋白通过其与肌动蛋白细胞骨架的相互作用为质膜提供机械稳定性，并间接地为细胞外基质蛋白提供机械稳定性。本研究旨在评价肌营养不良蛋白和钙蛋白酶-1在代偿性心肌肥厚向心力衰竭转变中的作用。Wistar大鼠进行腹主动脉缩窄，并在手术后30、60和90天（dps）处死。评价心功能和血压。收集心脏，并对肌营养不良蛋白、钙蛋白酶-1、α-胞衬蛋白和钙蛋白酶抑制蛋白进行蛋白质印迹和免疫荧光。进行统计分析，当p<0.05时认为是显著的。在90 dps后，70%的动物显示肥大心脏（HH）和30%的肥大+扩张心脏（HD）。HD组在30和60 dps时收缩和舒张功能保持不变，但下降。血压、心肌细胞直径和胶原含量在所有时间点均增加。在30和60 dps和HH组，Dystrophin表达轻度增加。HD组dystrophin和calpastatin表达减少，calpain-1和alpha-fodrin片段表达增加。早在60 dps时就观察到抗肌萎缩蛋白减少的第一个信号。总之，一些心脏在疾病的早期阶段呈现出独特的分子模式;这种模式可以为在心脏病发展过程中识别这些易衰竭心脏提供机会。我们发现，肌营养不良蛋白的表达减少和钙蛋白酶的表达增加是一致的，可以作为可能的治疗靶点，以防止心脏肥大导致的心力衰竭。
Hypertension causes cardiac hypertrophy, one of the most important risk factors for heart failure (HF). Despite the importance of cardiac hypertrophy as a risk factor for the development of HF, not all hypertrophied hearts will ultimately fail. Alterations of cytoskeletal and sarcolemma-associated proteins are considered markers cardiac remodeling during HF. Dystrophin provides mechanical stability to the plasma membrane through its interactions with the actin cytoskeleton and, indirectly, to extracellular matrix proteins. This study was undertaken to evaluate dystrophin and calpain-1 in the transition from compensated cardiac hypertrophy to HF. Wistar rats were subjected to abdominal aorta constriction and killed at 30, 60 and 90 days post surgery (dps). Cardiac function and blood pressure were evaluated. The hearts were collected and Western blotting and immunofluorescence performed for dystrophin, calpain-1, alpha-fodrin and calpastatin. Statistical analyses were performed and considered significant when p<0.05. After 90 dps, 70% of the animals showed hypertrophic hearts (HH) and 30% hypertrophic+dilated hearts (HD). Systolic and diastolic functions were preserved at 30 and 60 dps, however, decreased in the HD group. Blood pressure, cardiomyocyte diameter and collagen content were increased at all time points. Dystrophin expression was lightly increased at 30 and 60 dps and HH group. HD group showed decreased expression of dystrophin and calpastatin and increased expression of calpain-1 and alpha-fodrin fragments. The first signals of dystrophin reduction were observed as early as 60 dps. In conclusion, some hearts present a distinct molecular pattern at an early stage of the disease; this pattern could provide an opportunity to identify these failure-prone hearts during the development of the cardiac disease. We showed that decreased expression of dystrophin and increased expression of calpains are coincident and could work as possible therapeutic targets to prevent heart failure as a consequence of cardiac hypertrophy.
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DOI：
10.1111/j.1365-2613.2008.00604.x
发表时间：
2008-10-01
影响因子：
3
作者：
Campos, Erica C.;Romano, Minna M. D.;Rossi, Marcos A.
通讯作者：
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影响因子：
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作者：
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影响因子：
37.8
作者：
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通讯作者：
Molkentin JD
影响因子：
37.8
作者：
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通讯作者：
BING, OHL
影响因子：
5
作者：
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