Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
Cells. 2022 Apr 2;11(7):1199. doi: 10.3390/cells11071199.
PIEZO1 is a subunit of mechanically-activated, nonselective cation channels. Gain-of-function PIEZO1 mutations are associated with dehydrated hereditary stomatocytosis (DHS), a type of anaemia, due to abnormal red blood cell function. Here, we hypothesised additional effects on the heart. Consistent with this hypothesis, mice engineered to contain the M2241R mutation in PIEZO1 to mimic a DHS mutation had increased cardiac mass and interventricular septum thickness at 8-12 weeks of age, without altered cardiac contractility. Myocyte size was greater and there was increased expression of genes associated with cardiac hypertrophy (, and ). There was also cardiac fibrosis, increased expression of (a gene associated with fibrosis) and increased responses of isolated cardiac fibroblasts to PIEZO1 agonism. The data suggest detrimental effects of excess PIEZO1 activity on the heart, mediated in part by amplified PIEZO1 function in cardiac fibroblasts.
PIEZO1 是机械激活的非选择性阳离子通道的亚基。功能获得性 PIEZO1 突变与脱水遗传性口炎性腹泻（DHS）有关，这是一种贫血症，由于红细胞功能异常。在这里，我们假设对心脏有其他影响。与这一假设一致的是，工程设计的携带有 DHS 突变模拟的 PIEZO1 的 M2241R 突变的小鼠在 8-12 周龄时心脏质量和室间隔厚度增加，而心脏收缩力没有改变。心肌细胞大小增大，与心肌肥厚相关的基因表达增加（、和）。也有心脏纤维化，表达增加（与纤维化相关的基因），以及分离的心肌成纤维细胞对 PIEZO1 激动剂的反应增加。这些数据表明，过量 PIEZO1 活性对心脏有不利影响，部分原因是心脏成纤维细胞中 PIEZO1 功能增强。
