Can ARC save the heart?
Can ARC save the heart?
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ARC能拯救心脏吗？
DOI：
10.1016/j.jss.2009.07.016
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Abarbanell,AaronM
中科院分区：
文献类型：
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作者：
Abarbanell,AaronM
Ekhterae及其同事介绍了他们关于绵羊冠状动脉结扎后心肌细胞凋亡、心肌重塑和具有半胱天冬酶募集结构域（ARC）的凋亡抑制因子激活的研究结果。目前，ARC被认为几乎仅在心脏和骨骼肌中表达，并且已知ARC的激活抑制细胞凋亡[1]。之前，Donath等人观察到ARC缺陷小鼠在主动脉结扎后比同窝对照小鼠更快地发生心肌病。这些缺陷小鼠在缺血/再灌注损伤（I/R）后也有较大的梗死。两种观察结果均与心肌细胞凋亡增加相关[2]。因此，为了进一步阐述ARC与心肌重塑的时间相关性，Ekhterae及其同事在绵羊中诱导心尖梗死，并在结扎后2周、8周和32周通过2D回波获得功能数据。同时从梗死边缘区和远端区域进行活检。这些活组织切片被用来评估ARC激活和测量凋亡。在这个实验性心肌梗死（MI）模型中，左心室射血分数（EF）在结扎后2周和8周之间分别从32%下降到17%。正如预期的那样，收缩末期容积（ESV）在2周时增加了1.5倍基线，在8周时增加了2倍基线，表明发生了不良心室重塑。类似地，心肌细胞凋亡在两周时是明显的，并且在八周测量时继续增加。到32周，EF和ESV与8周相比没有显著变化，细胞凋亡减少。有趣的是，在边界区，激活的ARC在两周时升高，在八周时降低，并在32周时再次增加。当然，有人可能会说，如果总ARC水平在8周时下降，而不是2周和32周，可能会出现消费或生产问题。然而，总ARC水平没有显着差异的边界区。因此，降低的活化ARC水平可能与心室重塑和心肌细胞死亡有关。caspase-3和BAX水平进一步支持了这些相关性。这两种蛋白质都与细胞凋亡有关，并且两者的水平与激活的ARC水平呈负相关。
Ekhterae and colleagues present their findings regarding cardiomyocyte apoptosis, myocardial remodeling, and activation of the Apoptosis Repressor with Caspase Recruitment Domain (ARC) following coronary artery ligation in sheep. Currently, ARC is believed to be expressed almost exclusively in the heart and skeletal muscle, and activation of ARC is known to inhibit apoptosis [1]. Previously, Donath et al. observed that ARC deficient mice developed cardiomyopathy more rapidly than littermate controls after aortic banding. These deficient mice also had larger infarcts after ischemia/reperfusion injury (I/R). Both observations were associated with increased cardiomyocyte apoptosis [2]. Therefore to further elaborate on the temporal associations of ARC with respect to myocardial remodeling, Ekhterae and associates induced apical infarcts in sheep and obtained functional data by 2D echo at two, eight and 32 weeks post ligation. Concurrent biopsies were taken from the infarct border zone and a remote region. These biopsies were used to assess ARC activation and measure apoptosis.In this experimental model of myocardial infarction (MI), the left ventricular ejection fraction (EF) decreased between two and eight weeks post ligation from 32% to 17% respectively. As might be expected, the end systolic volume (ESV) was increased by a factor of 1.5 x baseline at two weeks and 2 x baseline at eight weeks indicating that adverse ventricular remodeling was occurring. Similarly cardiomyocyte apoptosis was evident at two weeks and continued to increase at the eight week measurement. By 32 weeks the EF and ESV had not changed significantly from eight weeks, and apoptosis was decreasing. Interestingly, activated ARC was elevated at two weeks, diminished at eight weeks and increased again at 32 weeks in the border zone. Certainly one could argue that if total ARC levels were decreased at eight weeks as compared to two and 32 weeks there may be a consumption or production issue. However, total ARC levels were not significantly different in the borderzone. Thus decreased levels of activated ARC may be linked to ventricular remodeling and myocyte death. These correlations are further supported by caspase-3 and BAX levels. Both proteins are associated with apoptosis, and the levels of both were inversely related to the level of activated ARC.