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Characterization of novel resident heart cells identified as atypically-shaped cardiomyocytes(ACMs)

被鉴定为非典型形状心肌细胞（ACM）的新型驻留心脏细胞的表征

基本信息

批准号：
22590204
负责人：
OMATSU Mariko
金额：
$ 2.91万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590204/
关键词：
ACMs novel heart cells self-beating atypically-shaped cardiomyocytes cardiomyocytes autophagy ischemia calcium transients novel heart cell cardiomyocyte cardiac ventricle Ca2+ transients automaticity atrial natriuretic peptide

项目摘要

We have investigated the presence of resident heart cells that are distinct from cardiomyocytes in adult mice. The heart was coronary perfused with enzymes and both ventricles were excised and further digested. After spinning the ventricular myocytes down, the supernatant fraction (cardiac myocyte-depleted fraction, CMDF) was cultured in methylcellulose-based semisolid culture medium. Three to five days after plating, some of the small cells adhered to the bottom of the dishes gradually developed their shapes and started beating spontaneously. These cells were mostly multinucleated, well sarcomeric-organized and expressed cardiac specific proteins, defined as a novel type of heart cells, atypically-shaped cardiomyocytes (ACMs). The cell population of ACMs was highest at neonatal period and significantly decreased within the first 5 weeks and reached a plateau in the adult stage. The ACMs obtained from both newborn and aged mice express the fetal cardiac gene products, such as atrial natriuretic peptide (ANP) and voltage-gated Ca2+channel CaV3.2. We examined whether CMDF cells, including ACMs, that underwent simulated lethal ischemia could develop into beating cells. When CMDF cells pre-exposed to ischemia were cultured for 6 days, the cell number of beating ACMs was ~50% of normoxic preparations. Electron microscopic analyses of ACMs displayed constitutively active autophagy during the culture even in the normoxic conditions. The results suggest the possibility that the development of beating ACMs could occur in injured heart, even if the surviving cell population is small.

我们已经调查了存在的常驻心脏细胞是不同于成年小鼠心肌细胞。用酶冠状灌注心脏，切除两个心室并进一步消化。将心室肌细胞旋转后，将上清液部分（心肌细胞耗尽部分，CMDF）在基于甲基纤维素的半固体培养基中培养。接种后3 - 5天，一些粘附在培养皿底部的小细胞逐渐发育出它们的形状，并开始自发跳动。这些细胞大多数是多核的，肌节组织良好，并表达心脏特异性蛋白，被定义为一种新型的心脏细胞，血管状心肌细胞（ACMs）。ACM的细胞数量在新生期最高，在前5周内显著下降，并在成年期达到平台期。从新生和老年小鼠获得的ACM表达胎儿心脏基因产物，如心房钠尿肽（ANP）和电压门控Ca 2+通道CaV3.2。我们研究了是否CMDF细胞，包括ACM，经历模拟致死性缺血可以发展成跳动的细胞。预先暴露于缺血的CMDF细胞培养6天后，搏动的ACM细胞数约为常氧制剂的50%。电子显微镜分析显示，即使在常氧条件下，在培养过程中的自噬活性组成。结果表明，即使存活的细胞群很小，也可能在受损的心脏中发生搏动的ACM的发展。