Reduced expression of adherens and gap junction proteins can have a fundamental role in the development of heart failure following cardiac hypertrophy in rats
Reduced expression of adherens and gap junction proteins can have a fundamental role in the development of heart failure following cardiac hypertrophy in rats
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DOI：
10.1016/j.yexmp.2015.12.009
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发表时间：
2016-02-01
影响因子：
3.6
通讯作者：
Prado, Cibele M.
中科院分区：
文献类型：
--
作者：
dos Santos, Daniele O.;Blefari, Valdecir;Prado, Cibele M.
高血压会导致心肌肥大、心功能不全和心力衰竭。从代偿性心肌肥厚向失代偿性心肌肥厚转变的机制尚不完全清楚。本研究旨在研究间盘蛋白表达的改变是否有助于从代偿性心肌肥厚到扩张性心脏发育的转变，最终导致心力衰竭。雄性大鼠采用腹主动脉缩窄模型，术后90d观察3组动物：假手术组(对照组)、肥厚组(HH)和肥厚+扩张组(HD)。对血压进行评估。收集心脏标本，进行桥粒芯糖蛋白-2、桥粒-粘连蛋白-2、N-钙粘蛋白、白蛋白、B-连环蛋白和连接蛋白-43的Western印迹和免疫荧光检测。用Vevo 2100超声系统评价心脏收缩功能。当P<；0.05的时候，数据被认为是重要的。在90DPS时，70%的动物患有HH，30%的动物患有HD。两组患者血压均升高。桥粒芯糖蛋白-2和桥粒芯糖蛋白-2的表达在两组均增加，但两组间无差异。高血压组N-钙粘蛋白、白蛋白、B-连环素表达增加，高血压组表达降低，连接蛋白-43表达仅在高血压组降低。射血分数和短轴缩短率在30DPS和60DPS时无差异，而HD组在90DPS时降低。我们发现，虽然在HH组中，随着细胞体积的增加而增加了一些蛋白的表达，但在HD组中，即使在与收缩功能下降相关的细胞体积没有明显减少的情况下，这些蛋白的表达也是减少的。桥粒芯糖蛋白-2和桥粒芯糖蛋白-2在HH组和HD组的表达增加，可能是一种保护性的代偿机制，有助于维持扩张的心脏。我们可以假设，与坏死和/或凋亡相关的不适当的细胞间机械和电气耦合是导致向HF过渡的重要因素。(C)2015 Elsevier Inc.保留所有权利。
Hypertension causes cardiac hypertrophy, cardiac dysfunction and heart failure (HF). The mechanisms implicated in the transition from compensated to decompensated cardiac hypertrophy are not fully understood. This study was aimed to investigate whether alterations in the expression of intercalated disk proteins could contribute to the transition of compensated cardiac hypertrophy to dilated heart development that culminates in HF. Male rats were submitted to abdominal aortic constriction and at 90 days post surgery (dps), three groups were observed: sham-operated animals (controls), animals with hypertrophic hearts (HH) and animals with hypertrophic + dilated hearts (HD). Blood pressure was evaluated. The hearts were collected and Western blot and immunofluorescence were performed to desmoglein-2, desmocollin-2, N-cadherin, plakoglobin, B-catenin, and connexin-43. Cardiac systolic function was evaluated using the Vevo 2100 ultrasound system. Data were considered significant when p < 0.05. Seventy percent of the animals presented with HH and 30% were HD at 90 dps. The blood pressure increased in both groups. The amount of desmoglein-2 and desmocollin-2 expression was increased in both groups and no difference was observed in either group. The expression of N-cadherin, plakoglobin and B-catenin increased in the HH group and decreased in the HD group; and connexin-43 decreased only in the HD group. There was no difference between the ejection fraction and fractional shortening at 30 and 60 dps; however, they were decreased in the HD group at 90 dps. We found that while some proteins have increased expression accompanied by the increase in the cell volume associated with preserved systolic cardiac function in the HH group, these same proteins had decreased expression even without significant reduction in the cell volume associated with decreased systolic cardiac function in HD group. The increased expression of desmoglein-2 and desmocollin-2 in both the HH and HD groups could work as a protective compensatory mechanism, helping to maintain the dilated heart. We can hypothesize that inappropriate intercellular mechanical and electrical coupling associated with necrosis and/or apoptosis are important factors contributing to the transition to HF. (C) 2015 Elsevier Inc All rights reserved.