Xie Dongmei, Liao Yan, Wu Binyuan, Chen Yang, Lin Wanwen, Lu Dihan, Gao Shanquan, Zhu Shuanghua, Peng Chaoquan, Jiang Mei Hua
Department of Cardiology, The Third Affiliated Hospital, Sun Yat-sen University.
Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University.
Int Heart J. 2018;59(1):180-189. doi: 10.1536/ihj.17-014.
Dilated cardiomyopathy (DCM), as one of the common cardiomyopathies, is a disease of the heart muscle; however, the etiology and pathogenesis of DCM were still poorly understood. Nestin has been reported a special marker of stem/progenitor cells in various tissues, and the tissue resident Nestin cells could promote the wound healing and tissue remodeling. However, it remains unclear whether Nestin cells participate in the protection of cardiomyocytes during the pathogenesis of DCM. Here the model of mice DCM was induced by doxorubicin (DOX) intraperitoneal injection and observed heart failure and ventricular enlargement via echocardiography and histologic analysis, respectively. During DCM pathogenesis, the number of Nestin cells showed a significant peak on day 6 after DOX treatment, which then gradually decreases to lower than normal levels after day 30 in the total population of the heart. Furthermore, we found that the isolated increased heart-derived Nestin cells are mesenchymal property and could protect DOX-induced HL-1 cells toxicity in vitro by promoting their proliferation and inhibiting their apoptosis. Collectively, our results showed that Nestin cells increased during DCM pathogenesis and played an important role in protecting against the DOX-induced HL-1 cells loss via regulating proliferation and apoptosis. Thus, the loss of Nestin cells might be an etiology to DCM pathogenesis, and these cells could be a promising candidate cell source for study and treatment of DCM patients.
扩张型心肌病（DCM）是常见的心肌病之一，是一种心肌疾病；然而，DCM的病因和发病机制仍未完全清楚。巢蛋白（Nestin）已被报道为各种组织中干细胞/祖细胞的一种特殊标志物，组织驻留的巢蛋白细胞可促进伤口愈合和组织重塑。然而，巢蛋白细胞在DCM发病机制中是否参与心肌细胞的保护作用仍不清楚。在此，通过腹腔注射阿霉素（DOX）诱导小鼠DCM模型，分别通过超声心动图和组织学分析观察心力衰竭和心室扩大情况。在DCM发病过程中，巢蛋白细胞数量在DOX治疗后第6天出现显著峰值，然后在第30天后在心脏总体细胞群中逐渐下降至低于正常水平。此外，我们发现分离出的增多的心脏来源的巢蛋白细胞具有间充质特性，并且在体外可通过促进DOX诱导的HL-1细胞增殖和抑制其凋亡来保护其免受毒性。总体而言，我们的结果表明，巢蛋白细胞在DCM发病过程中增多，并通过调节增殖和凋亡在防止DOX诱导的HL-1细胞损失中发挥重要作用。因此，巢蛋白细胞的缺失可能是DCM发病的一个病因，并且这些细胞可能是研究和治疗DCM患者的有前景的候选细胞来源。
