Transcriptomic profile analysis of the left atrium in spontaneously hypertensive rats at the early stage

Before morphological changes at the early stage of hypertension, how overloaded hypertension influences the transcriptomic profile of the left atrium remains unclear, therefore, RNA-sequencing was performed to define the RNA expressing profiles of left atrium in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) as a control group. At the same time, we compared the RNA expressing profiles changes in ARB-treated (valsartan, 30mg/kg/d) and ARNI-treated (sacubitril/valsartan, 60mg/kg/d) SHR to reveal the distinct effects on the left atrium. A total of 1558 differentially expressed genes were found in the left atrium between WKY rats and SHRs. Bioinformatics analysis revealed that these mRNAs could regulate the upstream pathways in atrial remodeling through atrial fibrosis, inflammation, electrical remodeling, and cardiac metabolism. The regulated transcripts of left atrial tissue in both the ARB-treated and ARNI-treated groups were related to metabolism. Compared with ARB, transcripts in ARNI-treated rats were mapped to the cGMP-PKG signaling pathway.在高血压早期形态学改变发生前，压力超负荷型高血压如何影响左心房转录组谱的机制仍未明确。为此，本研究采用RNA测序（RNA-sequencing）技术，明确自发性高血压大鼠（spontaneously hypertensive rats, SHR）以及作为对照的正常血压Wistar-Kyoto大鼠（Wistar-Kyoto rats, WKY）的左心房RNA表达谱。同时，本研究对比了经血管紧张素受体拮抗剂（ARB，缬沙坦，30mg/kg/d）与血管紧张素受体-脑啡肽酶抑制剂（ARNI，沙库巴曲缬沙坦，60mg/kg/d）干预的SHR的左心房RNA表达谱变化，以揭示两类药物对左心房的差异化作用效果。WKY大鼠与SHR的左心房组织中共鉴定出1558个差异表达基因（differentially expressed genes）。生物信息学分析显示，这些mRNA可通过心房纤维化、炎症反应、电重构及心脏代谢途径，调控心房重构的上游通路。ARB与ARNI干预组的左心房组织调控转录本均与代谢过程相关。与ARB干预组相比，ARNI干预组大鼠的转录本富集于cGMP-PKG信号通路。