Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Mol Med Rep. 2013 Nov;8(5):1343-52. doi: 10.3892/mmr.2013.1684. Epub 2013 Sep 13.
The aim of this study was to investigate the correlation between the change in the expression of atrial calpains and electrical, molecular and structural remodeling during aging and atrial fibrillation (AF). Adult and aged canines in sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were investigated. A whole-cell patch clamp was used to measure the L-type Ca2+ current (ICa-L) in cells in the left atrium. The mRNA and protein expression of the L-type calcium channel alc subunit (LVDCCa1c) and calpains were measured by quantitative (q)PCR and western blot analysis. Histopathological and ultrastructural changes were analyzed via light and electron microscopy. The quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial cells of the aged canines exhibited a longer action potential (AP) duration to 90% repolarization (APD90), lower AP plateau potential and peak ICa-L current densities (P<0.05). In the adult and aged groups, AF led to a higher maximum diastolic potential, an increase in AP amplitude and decreases in APD90, AP plateau potential and peak ICa-L densities (P<0.05). Compared with the control group, the mRNA and protein expression levels of LVDCCa1c were decreased in the aged groups; however, the mRNA and protein expression of calpain 1 was increased in the adult and the aged groups with AF (P<0.05). Samples of atrial tissue exhibited abnormal histopathological and ultrastructural changes, such as accelerated fibrosis and apoptosis with aging and in AF. Age-related alterations in atrial tissues were attributed to the increased expression of calpain 1. The general pathophysiological alterations in normal aged atria may therefore produce a substrate that is conducive to AF.
本研究旨在探讨心房钙蛋白酶表达的变化与衰老和心房颤动（AF）期间电、分子和结构重构之间的相关性。研究了窦性心律（SR）和持续性 AF（通过快速心房起搏诱导）的成年和老年犬。使用全细胞膜片钳技术测量左心房细胞中的 L 型钙电流（ICa-L）。通过定量（q）PCR 和 Western blot 分析测量 L 型钙通道 alc 亚基（LVDCCa1c）和钙蛋白酶的 mRNA 和蛋白表达。通过光镜和电子显微镜分析组织病理学和超微结构变化。通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）测定法确定凋亡心肌细胞的数量。在 SR 组中，老年犬的心房细胞表现出更长的动作电位（AP）复极至 90%（APD90）持续时间、更低的 AP 平台电位和峰值 ICa-L 电流密度（P<0.05）。在成年和老年组中，AF 导致最大舒张电位更高、AP 幅度增加以及 APD90、AP 平台电位和峰值 ICa-L 密度降低（P<0.05）。与对照组相比，老年组 LVDCCa1c 的 mRNA 和蛋白表达水平降低；然而，在有 AF 的成年和老年组中，钙蛋白酶 1 的 mRNA 和蛋白表达增加（P<0.05）。心房组织样本表现出异常的组织病理学和超微结构变化，如纤维化和凋亡加速与衰老和 AF 有关。心房组织与年龄相关的改变归因于钙蛋白酶 1 的表达增加。因此，正常老年心房的一般病理生理改变可能产生有利于 AF 的基质。
