心肌梗死后短期阻断S100A9有利于调节心肌ATP的产生和收缩力

IF 13 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Raluca M. Boteanu, Viorel I. Suica, Elena Uyy, Luminita Ivan, Diana V. Uta, Razvan G. Mares, Maya Simionescu, Alexandru Schiopu, Felicia Antohe
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引用次数: 0

摘要

梗塞的心脏能量受损,表现为三磷酸腺苷(ATP)产生不足,随后收缩功能受损。短期阻断S100A9蛋白可改善小鼠心肌梗死(MI)后的心脏功能。在这个过程中对ATP产生的影响尚不清楚。目的观察S100A9阻断对心肌梗死后7天C57BL/6小鼠ATP合成和心肌收缩力的影响。方法采用永久性左冠状动脉结扎致心肌梗死小鼠、S100A9阻断剂ABR-238901短期治疗心肌梗死小鼠和假手术(对照组)小鼠三组。切除左心室后,进行质谱分析、途径富集分析、Western blot、RT-PCR和药理网络分析。结果与心肌梗死小鼠相比,S100A9阻断剂显著改变了心肌梗死小鼠体内600种差异丰度蛋白(DAPs)的数量。其中一些蛋白与氧化磷酸化、柠檬酸循环(TCA)、线粒体脂肪酸β -氧化、糖酵解和心肌收缩途径有关。在缺血性脑室中,ABR-238901使NDUFAB1、UQCRC1、HADHA、ACAA2、ALDOA、PKM1、DLD、DLAT、PDHX、ACO2、IDH3A、FH1、CKM、CKMT2、TNNC1等蛋白丰度增加(1.8- 38倍),这些蛋白对细胞早期代谢变化、ATP分布和收缩性至关重要。与心肌梗死小鼠相比,ABR-238901处理后心肌ATP水平升高(1.8倍,p <; 0.05)。网络药理学分析揭示了ABR-238901的潜在药理学靶点,这些靶点可能与ATP产生和收缩性相关的DAPs相互作用。结论短期阻断S100A9可有效调节心肌梗死后ATP生成和心肌收缩力相关蛋白,为心肌能量代谢研究提供了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Cardiac ATP production and contractility are favorably regulated by short-term S100A9 blockade after myocardial infarction

Cardiac ATP production and contractility are favorably regulated by short-term S100A9 blockade after myocardial infarction

Introduction

The infarcted heart is energetically compromised exhibiting a deficient production of adenosine triphosphate (ATP) and the ensuing impaired contractile function. Short-term blockade of the protein S100A9 improves cardiac performance in mice after myocardial infarction (MI). The implications upon ATP production during this process are not known.

Objectives

This study evaluates whether S100A9 blockade effects ATP synthesis and cardiac contractility in C57BL/6 mice at seven days post-MI.

Methods

Three experimental groups were used: (i) mice with MI, induced by permanent left coronary ligation, (ii) mice with MI, short-term treated with the S100A9 blocker ABR-238901, and (iii) sham (control) mice. After removing the left ventricle, mass spectrometry, pathway enrichment analysis, Western blot, RT-PCR and pharmacological network analysis were performed.

Results

A number of 600 differential abundance proteins (DAPs) was significantly altered by the S100A9 blocker in MI-treated mice compared with MI mice. Some of these proteins were associated with oxidative phosphorylation, citrate cycle (TCA), mitochondrial fatty acid beta-oxidation, glycolysis and cardiac muscle contraction pathways. In the ischemic ventricle, ABR-238901 treatment increased (1.8- to 38-fold) the abundance of proteins NDUFAB1, UQCRC1, HADHA, ACAA2, ALDOA, PKM1, DLD, DLAT, PDHX, ACO2, IDH3A, FH1, CKM, CKMT2, TNNC1, crucial for early cellular metabolic changes, ATP distribution and contractility. The cardiac level of ATP increased (1.8-fold, p < 0.05) in MI mice treated with ABR-238901 compared to MI mice. The network pharmacology analysis uncovered potential pharmacologic targets of ABR-238901 that may interact with DAPs related to ATP production and contractility.

Conclusion

Short-term S100A9 blockade effectively regulates the proteins implicated in ATP production and cardiac contractility post-MI, providing a framework for future cardiac energy metabolism studies.
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来源期刊
Journal of Advanced Research
Journal of Advanced Research Multidisciplinary-Multidisciplinary
CiteScore
21.60
自引率
0.90%
发文量
280
审稿时长
12 weeks
期刊介绍: Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.
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