Altered ventricular torsion and transmural patterns of myocyte relaxation precede heart failure in aging F344 rats
Altered ventricular torsion and transmural patterns of myocyte relaxation precede heart failure in aging F344 rats
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DOI：
10.1152/ajpheart.00797.2012
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发表时间：
2013-09-01
影响因子：
4.8
通讯作者：
Campbell, Kenneth S.
中科院分区：
文献类型：
--
作者：
Campbell, Stuart G.;Haynes, Premi;Campbell, Kenneth S.
本研究的目的是确定和解释心室和细胞功能的变化，有助于衰老相关的心血管疾病在老龄F344大鼠。研究了三组雌性F344大鼠，年龄分别为6、18和22个月。异氟醚麻醉动物的超声心动图测量显示，6月龄和18月龄组之间的左室扭转峰值增加，而22月龄组部分逆转（P < 0.05）。随后从每组大鼠的左心室分离心外膜、中层心肌和内膜心肌细胞。然后在这些细胞中测量未加载的肌节缩短和Ca2+瞬变（对于九个年龄区域组中的每一个，n = >75个细胞）。Ca2+瞬变衰减时间和50%长度松弛所需时间均随年龄增长而增加，但在三个区域中并不均匀（P < 0.02）。进一步的分析显示，这些属性的透壁分布在18和22个月的年龄之间的显着变化，最大的变化发生在心外膜肌细胞。计算模型表明，这些变化部分是由于老化的心外膜肌细胞中肌钙蛋白的Ca2+解离较慢。随后的生化分析显示，相对于其他区域，22月龄心外膜肌钙蛋白I磷蛋白含量减少>50%。这些数据表明，在18至22月龄（心力衰竭发作前），F344大鼠显示心外膜特异性肌张力水平改变，1）从6至18月龄观察到的进展中断，2）与心脏扭转的异常模式一致。
The purpose of this study was to identify and explain changes in ventricular and cellular function that contribute to aging-associated cardiovascular disease in aging F344 rats. Three groups of female F344 rats, aged 6, 18, and 22 mo, were studied. Echocardiographic measurements in isoflurane-anesthetized animals showed an increase in peak left ventricular torsion between the 6- and the 18-mo-old groups that was partially reversed in the 22-mo-old animals (P < 0.05). Epicardial, midmyocardial, and endocardial myocytes were subsequently isolated from the left ventricles of each group of rats. Unloaded sarcomere shortening and Ca2+ transients were then measured in these cells (n = >75 cells for each of the nine age-region groups). The decay time of the Ca2+ transient and the time required for 50% length relaxation both increased with age but not uniformly across the three regions (P < 0.02). Further analysis revealed a significant shift in the transmural distribution of these properties between 18 and 22 mo of age, with the largest changes occurring in epicardial myocytes. Computational modeling suggested that these changes were due in part to slower Ca2+ dissociation from troponin in aging epicardial myocytes. Subsequent biochemical assays revealed a >50% reduction in troponin I phosphoprotein content in 22-mo-old epicardium relative to the other regions. These data suggest that between 18 and 22 mo of age (before the onset of heart failure), F344 rats display epicardial-specific myofilament-level modifications that 1) break from the progression observed between 6 and 18 mo and 2) coincide with aberrant patterns of cardiac torsion.