Aspirin and Celecoxib Regulate Notch1/Hes1 Pathway to Prevent Pressure Overload-Induced Myocardial Hypertrophy

IF 1.2 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Minghui Wei, Ziyu Lu, Haifeng Zhang, Xiaomei Fan, Xin Zhang, Bihui Jiang, Jianying Li, Mingming Xue
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引用次数: 0

Abstract

This study aimed to investigate the molecular mechanisms underlying the protective effects of cyclooxygenase (cox) inhibitors against myocardial hypertrophy.

Rat H9c2 cardiomyocytes were induced by mechanical stretching. SD rats underwent transverse aortic constriction to induce pressure overload myocardial hypertrophy. Rats were subjected to echocardiography and tail arterial pressure in 12W. qPCR and western blot were used to detect the expression of Notch-related signaling. The inflammatory factors were tested by ELISA in serum, heart tissue, and cell culture supernatant.

Compared with control, levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β were increased and anti-inflammatory cytokine IL-10 was reduced in myocardial tissues and serum of rat models. Levels of Notch1 and Hes1 were reduced in myocardial tissues. However, cox inhibitor treatment (aspirin and celecoxib), the improvement of exacerbated myocardial hypertrophy, fibrosis, dysfunction, and inflammation was parallel to the activation of Notch1/Hes1 pathway. Moreover, in vitro experiments showed that, in cardiomyocyte H9c2 cells, application of ~20% mechanical stretching activated inflammatory mediators (IL-6, TNF-α, and IL-1β) and hypertrophic markers (ANP and BNP). Moreover, expression levels of Notch1 and Hes1 were decreased. These changes were effectively alleviated by aspirin and celecoxib.

Cox inhibitors may protect heart from hypertrophy and inflammation possibly via the Notch1/Hes1 signaling pathway.

阿司匹林和塞来昔布调节Notch1/Hes1通路,预防压力过载诱发的心肌肥厚
本研究旨在探讨环氧化酶(cox)抑制剂对心肌肥厚具有保护作用的分子机制。对 SD 大鼠进行横向主动脉收缩以诱导压力超负荷心肌肥厚。用 qPCR 和 western blot 检测 Notch 相关信号的表达。与对照组相比,模型大鼠心肌组织和血清中的促炎细胞因子IL-6、TNF-α和IL-1β水平升高,抗炎细胞因子IL-10水平降低。心肌组织中 Notch1 和 Hes1 的水平降低。然而,cox 抑制剂治疗(阿司匹林和塞来昔布)对加重的心肌肥厚、纤维化、功能障碍和炎症的改善与 Notch1/Hes1 通路的激活是平行的。此外,体外实验表明,在心肌细胞 H9c2 中,施加约 20% 的机械拉伸可激活炎症介质(IL-6、TNF-α 和 IL-1β)和肥大标志物(ANP 和 BNP)。此外,Notch1 和 Hes1 的表达水平也有所下降。Cox抑制剂可能通过Notch1/Hes1信号通路保护心脏免受肥厚和炎症的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International heart journal
International heart journal 医学-心血管系统
CiteScore
2.50
自引率
6.70%
发文量
148
审稿时长
6-12 weeks
期刊介绍: Authors of research articles should disclose at the time of submission any financial arrangement they may have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Such information will be held in confidence while the paper is under review and will not influence the editorial decision, but if the article is accepted for publication, the editors will usually discuss with the authors the manner in which such information is to be communicated to the reader.
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