Detection of TUNEL-positive cardiomyocytes and C-kit-positive progenitor cells in children with congenital heart disease
Detection of TUNEL-positive cardiomyocytes and C-kit-positive progenitor cells in children with congenital heart disease
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DOI：
10.1016/j.yjmcc.2007.05.011
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发表时间：
2007-09-01
影响因子：
5
通讯作者：
Hamaoka, Kenji
中科院分区：
文献类型：
--
作者：
Sato, Hisashi;Shiraishi, Isao;Hamaoka, Kenji
心肌细胞因凋亡而丧失以及随后被纤维结缔组织替代是成人心脏病中心脏重塑的重要特征。然而，在患有 CHID 的儿童中，由于解剖学和血流动力学的复杂性，心力衰竭的细胞和分子机制尚未完全了解。为了研究先天性心脏病 (CHD) 儿童心肌细胞的凋亡死亡和心脏祖细胞的动员，进行了末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 测定和抗 c-kit 抗体的免疫组织化学分析。 CHD 儿童 (n= 17) 中 TUNEL 阳性心肌细胞的发生率 (0.39 +/- 0.21%) 高于儿童对照 (0.072 +/- 0.037%, p < 0.001, n=6)，但其发生率低于成人心脏病患者 (1.35 +/- 0.54%,p < 0.005, n = 7)。在患有先心病的儿童中未观察到显着的心肌细胞肥大或纤维化。血流动力学表现出容量超负荷的 CHD 患者比严重紫绀患者 (0.20 +/- 0.12%,p < 0.05, n = 4) 具有更多的 TUNEL 阳性心肌细胞 (0.58 +/- 0.17%, n = 4)。与儿童对照 (p < 0.01) 和患有心脏病的成人 (p < 0.005) 相比，CHD 中检测到的 C-kit 阳性细胞更为丰富。 c-kit阳性细胞的发生率与TUNEL阳性心肌细胞的发生率相关（r=0.513）。与成年心脏病患者相比，心肌细胞凋亡和随后被纤维结缔组织替代是重塑过程的特征，而患有先心病的儿童的压力被发现较少诱导心肌细胞凋亡和纤维化。这项研究还提供了 CHD 儿童心肌细胞凋亡与 c-kit 阳性细胞动员之间的可能关系。 (c) 2007 Elsevier Inc. 保留所有权利。
The loss of cardiornyocytes by apoptosis and the subsequent replacement by fibrous connective tissues are important features of cardiac remodeling in adult heart disease. In children with CHID, however, the cellular and molecular mechanisms of heart failure have not yet been fully understood because of the anatomical and hemodynamic complexities. To investigate the apoptotic death of cardiornyocytes and mobilization of cardiac progenitor cells in children with congenital heart disease (CHD), terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) assay and immunohistochemistry with antibody against c-kit were performed. The incidence of TUNEL-positive cardiomyocytes in children with CHD (n= 17) was higher (0.39 +/- 0.21%) than that in the child controls (0.072 +/- 0.037%, p < 0.001, n=6), however, the incidence was lower than that in adults with heart disease (1.35 +/- 0.54%,p < 0.005, n = 7). Significant cardiomyocyte hypertrophy or fibrosis was not observed in children with CHD. The CHD patients hemodynamically demonstrating a volume overload showed more TUNEL-positive cardiornyocytes (0.58 +/- 0.17%, n = 4) than those with severe cyanosis (0.20 +/- 0.12%,p < 0.05, n = 4). C-kit-positive cells were more abundantly detected in CHD in comparison to the child control (p < 0.01) and the adults with heart disease (p < 0.005). The incidence of c-kit-positive cells correlated with that of TUNEL-positive cardiomyocytes (r=0.513). In contrast to adult patients with heart disease where cardiomyocyte apoptosis and the subsequent replacement by fibrous connective tissue are characteristic features of remodeling process, stress in children with CHD was found to induce less cardiomyocyte apoptosis and fibrosis. This study also provides a possible relationship between cardiomyocyte apoptosis and mobilization of c-kit-positive cells in children with CHD. (c) 2007 Elsevier Inc. All rights reserved.