Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Edinburgh Preclinical Imaging, Edinburgh Preclinical Imaging, BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Int J Mol Sci. 2021 Jan 19;22(2):969. doi: 10.3390/ijms22020969.
Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR (small regulatory polypeptide of amino acid response) locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression, we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line. We investigated post-natal growth and development, basal cardiac function, the cardiac functional response, and tissue-specific response to myocardial infarction. To investigate the influence of the LINC00961/SPAAR locus on longitudinal growth, cardiac function, and response to myocardial infarction, we used a novel CRISPR/Cas9 locus knockout mouse line. Data mining suggested that SPAAR is predominantly expressed in human cardiac endothelial cells and fibroblasts, while murine LINC00961 expression is hypoxia-responsive in mouse endothelial cells. LINC00961 mice displayed a sex-specific delay in longitudinal growth and development, smaller left ventricular systolic and diastolic areas and volumes, and greater risk area following myocardial infarction compared with wildtype littermates. These data suggest the LINC00961/SPAAR locus contributes to cardiac endothelial cell and fibroblast function and hypoxic response, growth and development, and basal cardiovascular function in adulthood.
长链非编码 RNA（lncRNA）在发育和疾病中具有结构和功能作用。我们之前已经表明，LINC00961/SPAAR（氨基酸反应的小调节多肽）基因座调节内皮细胞功能，并且该 lncRNA 和微肽都可以反向调节血管生成。为了评估人类心脏细胞 SPAAR 的表达，我们挖掘了一个公开的 scRNSeq 数据集，并在鼠内皮细胞系中证实了 LINC00961 基因座的表达和缺氧反应。我们研究了出生后的生长和发育、基础心脏功能、心脏功能反应以及心肌梗死的组织特异性反应。为了研究 LINC00961/SPAAR 基因座对纵向生长、心脏功能和心肌梗死反应的影响，我们使用了一种新型的 CRISPR/Cas9 基因座敲除小鼠系。数据挖掘表明，SPAAR 主要在人类心脏内皮细胞和成纤维细胞中表达，而鼠 LINC00961 表达在鼠内皮细胞中对缺氧有反应。与野生型同窝仔相比，LINC00961 小鼠表现出纵向生长和发育的性别特异性延迟、左心室收缩和舒张面积及体积更小，以及心肌梗死后的危险面积更大。这些数据表明，LINC00961/SPAAR 基因座有助于心脏内皮细胞和成纤维细胞功能以及缺氧反应、生长和发育以及成年期基础心血管功能。
