The difference of right and left ventricular remodeling caused by volume overload in neonatal SD rats

We reported the RNAseq analyses of right ventricle (RV) and left ventricle (LV) in neonatal volume overload (VO) and sham-operated SD rat. VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) within 24 hours postnatally (P1). RNAseq analyses of RV and LV free wall of P7 from VO and sham-operated rat. It demonstrated that the 1806 differentially expressed genes (DEGs) between RV and LV at the neonatal stage were primarily enriched in GTPase mediating signal transduction, insulin signaling pathway and thyroid hormone signaling pathway. VO produced 3 more times DEGs in LV than RV . GO analysis of these DEGs demonstrated that in the top 150 enriched terms, the LV comparison and RV comparison shared 34 terms (22.7%) in common. These commonly enriched terms were primarily associated with GTPase mediating signal transduction. KEGG analysis of these DEGs demonstrated that in the top 30 enriched terms, the LV comparison and RV comparison shared 14 terms (46.7%) in common. And insulin signaling pathway and thyroid hormone signaling pathway are the top two enriched terms in common. Regarding the differently enriched GO terms, they were primarily associated with lipid metabolism and ion channel in RV and primarily associated nucleic acid metabolism in LV. The top two differently enriched KEGG terms were arrhythmogenic right ventricular cardiomyopathy (ARVC) and adipocytokine signaling pathway in RV while microRNAs in cancer and longevity regulating pathway in LV. These results were further confirmed by the determination of metabolites.本研究报道了新生期容量超负荷（neonatal volume overload, VO）与假手术SD大鼠的右心室（right ventricle, RV）、左心室（left ventricle, LV）RNA测序（RNAseq）分析结果。该新生期容量超负荷模型于大鼠出生后24小时内（即出生后第1天，P1）通过腹主动脉与下腔静脉之间的瘘管（abdominal aorta and inferior vena cava fistula, AVF）诱导构建。本研究同时对出生后第7天（P7）的VO模型组与假手术组大鼠的右心室游离壁、左心室游离壁开展了RNAseq分析。分析结果显示，新生期大鼠右心室与左心室间共存在1806个差异表达基因（differentially expressed genes, DEGs），这些基因主要富集于GTP酶（GTPase）介导的信号转导（signal transduction）、胰岛素信号通路（insulin signaling pathway）及甲状腺激素信号通路（thyroid hormone signaling pathway）。VO模型组大鼠左心室的差异表达基因数量约为右心室的3倍。对上述差异表达基因进行基因本体（Gene Ontology, GO）富集分析后发现，在排名前150的富集条目中，左心室比较组与右心室比较组共存在34个共有富集条目，占比达22.7%，这些共有富集条目主要与GTP酶介导的信号转导通路相关。对上述差异表达基因开展京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析结果显示，在排名前30的富集条目中，左心室比较组与右心室比较组共存在14个共有富集条目，占比达46.7%，其中胰岛素信号通路与甲状腺激素信号通路为两组共有的前两位富集条目。针对两组间差异富集的GO条目，右心室相关比较组的特有富集条目主要与脂质代谢及离子通道相关，左心室相关比较组的特有富集条目则主要与核酸代谢相关；右心室相关比较组中排名前两位的差异富集KEGG条目为致心律失常性右心室心肌病（arrhythmogenic right ventricular cardiomyopathy, ARVC）与脂肪细胞因子信号通路（adipocytokine signaling pathway），左心室相关比较组中则为癌症相关microRNA通路与寿命调控通路（longevity regulating pathway）。上述研究结果通过代谢物（metabolites）检测得到了进一步验证。