Dapagliflozin attenuates myocardial remodeling in hypertension by activating the circadian rhythm signaling pathway

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Jing Wang, Qiang She, Jianlin Du
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引用次数: 3

Abstract

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new kind of antidiabetic drug which has shown beneficial effects in reducing heart failure-related hospitalization and cardiovascular-related mortality. The mechanisms are complicated. Our study aimed to investigate the effects of dapagliflozin on the myocardium of spontaneously hypertensive rats (SHRs) without heart failure. Wistar-Kyoto rats were used as normal controls. SHRs were randomly divided into the SHR group and the -treated group. After 8 weeks of dapagliflozin treatment, the morphology of heart tissues was examined. The mRNA expression profiles were identified via RNA sequencing (RNA-Seq). Various analysis methods were used to find the differentially expressed genes (DEGs) to predict gene function and coexpression. After dapagliflozin treatment, systolic blood pressure was significantly reduced compared with that in the SHR group. Myocardial remodeling was ameliorated compared with that in the SHR group. After dapagliflozin intervention, 75 DEGs (|log2-fold change | > 0 and Q value < 0.05) were identified in the heart tissues compared to the SHR group. Quantitative real-time PCR analysis confirmed that the expression of the circadian rhythm genes Per3, Bhlhe41, and Nr1d1 was significantly upregulated, while the results were coincident with the RNA-Seq results. Dapagliflozin may effectively inhibit myocardial remodeling and regulate blood pressure. The mechanisms may be related to the activation of the circadian rhythm signaling pathway.

Abstract Image

达格列嗪通过激活昼夜节律信号通路来减轻高血压患者的心肌重塑。
钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)是一种新型的抗糖尿病药物,在降低心力衰竭相关住院和心血管相关死亡率方面显示出有益的效果。机制是复杂的。本研究旨在研究达格列嗪对无心力衰竭的自发性高血压大鼠(SHR)心肌的影响。Wistar Kyoto大鼠作为正常对照。将SHR随机分为SHR组和治疗组。达格列嗪治疗8周后,检查心脏组织的形态学。通过RNA测序(RNA-Seq)鉴定mRNA表达谱。使用各种分析方法来寻找差异表达基因(DEGs),以预测基因功能和共表达。达格列嗪治疗后,收缩压与SHR组相比显著降低。与SHR组相比,心肌重构得到改善。达格列嗪干预后,75 DEG(|log2倍变化|>0和Q值
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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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