Ma Jian, Xin Xumin, Jia Yuewang, Deng Haijun, Liu Mengmeng, Jiang Yonghong, Du Jianlin
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Chongqing, 400010, China.
Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 23. doi: 10.1007/s00210-024-03775-4.
Angiotensin receptor-neprilysin inhibitor (ARNI) and angiotensin II receptor blockers (ARB) are antihypertension medications that improve cardiac remodeling and protect the heart. However, at the early stage of hypertension, it is still unclear how these two drugs affect the transcriptomic profile of multiple organs in hypertensive rats and the transcriptomic differences between them. We performed RNA sequencing to define the RNA expressing profiles of the eight tissues (atrium, ventricle, aorta, kidney, brain, lung, white fat, and brown fat) in spontaneously hypertensive rats (SHRs) and SHRs treated with ARNI or ARB. Acquired data was processed and analyzed by computational analyses (i.e., clustering, DEG, functional association, WGCNA, and protein-protein interaction (PPI) network analysis). We discovered that various tissues produced significant transcriptomic changes at the early stage of hypertension. The transcriptomic differences are notably in brown fat, kidney, lung, and brain tissues between ARNI and ARB treatment. Meanwhile, ARNI or ARB treatment can reverse the dysregulated expression genes related to the metabolism process, especially in brown fat, lung, and kidney tissues under hypertension. The current study has presented a comprehensive rat RNA-Seq transcriptomic landscape in SHRs and compared the transcriptome differences between ARNI and ARB treatment as a biomedical research resource for further study.
血管紧张素受体脑啡肽酶抑制剂(ARNI)和血管紧张素II受体阻滞剂(ARB)是可改善心脏重塑并保护心脏的抗高血压药物。然而,在高血压早期,这两种药物如何影响高血压大鼠多个器官的转录组谱以及它们之间的转录组差异仍不清楚。我们进行了RNA测序,以确定自发性高血压大鼠(SHR)以及接受ARNI或ARB治疗的SHR的八个组织(心房、心室、主动脉、肾脏、大脑、肺、白色脂肪和棕色脂肪)的RNA表达谱。通过计算分析(即聚类、差异表达基因分析、功能关联分析、加权基因共表达网络分析和蛋白质-蛋白质相互作用(PPI)网络分析)对获得的数据进行处理和分析。我们发现,在高血压早期,各种组织产生了显著的转录组变化。ARNI和ARB治疗之间的转录组差异在棕色脂肪、肾脏、肺和脑组织中尤为明显。同时,ARNI或ARB治疗可逆转与代谢过程相关的失调表达基因,尤其是在高血压状态下的棕色脂肪、肺和肾脏组织中。本研究展示了SHR全面的大鼠RNA测序转录组图谱,并比较了ARNI和ARB治疗之间的转录组差异,作为进一步研究的生物医学研究资源。