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Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload
Cell Death Discovery ( IF 7 ) Pub Date : 2021-08-07 , DOI: 10.1038/s41420-021-00593-y
Chunxia Zhou 1 , Sijuan Sun 2 , Mengyu Hu 3 , Yingying Xiao 1 , Xiafeng Yu 1 , Lincai Ye 1, 4, 5 , Lisheng Qiu 1
Affiliation  

The molecular atlas of postnatal mouse ventricular development has been made available and cardiac regeneration is documented to be a downregulated process. The right ventricle (RV) differs from the left ventricle. How volume overload (VO), a common pathologic state in children with congenital heart disease, affects the downregulated processes of the RV is currently unclear. We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 7 (P7) using a mouse model to induce a prepubertal RV VO. RNAseq analysis of RV (from postnatal day 14 to 21) demonstrated that angiogenesis was the most enriched gene ontology (GO) term in both the sham and VO groups. Regulation of the mitotic cell cycle was the second-most enriched GO term in the VO group but it was not in the list of enriched GO terms in the sham group. In addition, the number of Ki67-positive cardiomyocytes increased approximately 20-fold in the VO group compared to the sham group. The intensity of the vascular endothelial cells also changed dramatically over time in both groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the downregulated transcriptome revealed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway was replaced by the cell cycle in the top-20 enriched KEGG terms because of the VO. Angiogenesis was one of the primary downregulated processes in postnatal RV development, and the cell cycle was reactivated under the influence of VO. The mechanism underlying the effects we observed may be associated with the replacement of the PPAR-signaling pathway with the cell-cycle pathway.



中文翻译:

在容量过载的影响下,出生后右心室的发育过程下调

出生后小鼠心室发育的分子图谱已经可用,心脏再生被证明是一个下调过程。右心室 (RV) 不同于左心室。先天性心脏病儿童常见的病理状态容量超负荷 (VO) 如何影响 RV 的下调过程,目前尚不清楚。我们在产后第 7 天 (P7) 使用小鼠模型在腹主动脉和下腔静脉之间创建了一个瘘管,以诱导青春期前 RV VO。RV(从出生后第 14 天到第 21 天)的 RNAseq 分析表明,血管生成是假手术组和 VO 组中最丰富的基因本体 (GO) 术语。有丝分裂细胞周期的调节是 VO 组中第二丰富的 GO 术语,但它不在假手术组中丰富的 GO 术语列表中。此外,与假手术组相比,VO 组中 Ki67 阳性心肌细胞的数量增加了约 20 倍。两组血管内皮细胞的强度也随时间发生了显着变化。京都基因和基因组百科全书 (KEGG) 对下调转录组的通路分析显示,由于 VO,过氧化物酶体增殖物激活受体 (PPAR) 信号通路被前 20 个富集 KEGG 术语中的细胞周期所取代。血管生成是出生后 RV 发育的主要下调过程之一,细胞周期在 VO 的影响下重新激活。我们观察到的影响的潜在机制可能与用细胞周期通路替代 PPAR 信号通路有关。

更新日期:2021-08-09
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