RNA-Seq transcriptomic landscape profiling of spontaneously hypertensive rats in youth treated with a ARNI versus ARB.

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-07-01 Epub Date: 2025-01-23 DOI:10.1007/s00210-024-03775-4
Jian Ma, Xumin Xin, Yuewang Jia, Haijun Deng, Mengmeng Liu, Yonghong Jiang, Jianlin Du
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Abstract

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.

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ARNI与ARB治疗的青年自发性高血压大鼠的RNA-Seq转录组景观分析。
血管紧张素受体-neprilysin抑制剂(ARNI)和血管紧张素II受体阻滞剂(ARB)是改善心脏重塑和保护心脏的降压药物。然而,在高血压早期,这两种药物如何影响高血压大鼠多器官的转录组谱以及它们之间的转录组差异尚不清楚。我们对自发性高血压大鼠(SHRs)和接受ARNI或ARB治疗的shs进行了RNA测序,以确定8个组织(心房、心室、主动脉、肾脏、脑、肺、白色脂肪和棕色脂肪)的RNA表达谱。获取的数据通过计算分析(即聚类、DEG、功能关联、WGCNA和蛋白-蛋白相互作用(PPI)网络分析)进行处理和分析。我们发现,在高血压早期,各种组织都发生了显著的转录组变化。ARNI和ARB治疗在棕色脂肪、肾脏、肺和脑组织中的转录组差异显著。同时,ARNI或ARB治疗可以逆转与代谢过程相关的异常表达基因,特别是在高血压患者的棕色脂肪、肺和肾组织中。本研究提出了SHRs中大鼠RNA-Seq转录组的综合景观,并比较了ARNI和ARB治疗的转录组差异,作为进一步研究的生物医学研究资源。
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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
142
审稿时长
4-8 weeks
期刊介绍: Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
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