肾素-血管紧张素系统的非经典轴和Neprilysin:代谢综合征模型中心肌缺血时ppar - α激活的心脏保护作用的关键介质。

IF 3.5 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL PPAR Research Pub Date : 2020-11-27 eCollection Date: 2020-01-01 DOI:10.1155/2020/8894525
María Sánchez-Aguilar, Luz Ibarra-Lara, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Juan Carlos Torres-Narváez, Elizabeth Carreón-Torres, Alicia Sánchez-Mendoza, María Esther Rubio-Ruíz
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引用次数: 2

摘要

肾素-血管紧张素系统(RAS)的激活参与代谢综合征(MetS)和心力衰竭的发展。非诺贝特激活ppar - α可以逆转由这些病理引起的一些影响。最近,非经典RAS成分被认为与高血压和心肌功能障碍的发病机制有关;然而,它们的心脏功能仍然存在争议。我们评估了由血管紧张素III和血管紧张素-(1-7)引导的非经典RAS信号通路是否参与了非诺贝特在MetS大鼠缺血期间的心脏保护作用。对照(CT)和MetS大鼠分为以下组:(a)假手术组,(b)载药治疗的心肌梗死(MI-V)组,(c)非诺贝特治疗的心肌梗死(MI-F)组。血管紧张素III和血管紧张素IV水平和胰岛素增加了氨肽酶(IRAP)的表达,降低了血管紧张素转换酶2 (ACE2)的表达。缺血激活血管紧张素转换酶(ACE)/血管紧张素II/血管紧张素受体1 (AT1R)和血管紧张素III/血管紧张素IV/血管紧张素受体4 (AT4R)-IRAP轴。非诺贝特治疗通过促进血管紧张素-(1-7)/血管紧张素受体2 (AT2R)轴和抑制血管紧张素III/血管紧张素IV/AT4R-IRAP信号通路来预防MetS大鼠缺血损伤。此外,非诺贝特下调了neprilysin的表达,增加了缓激肽的产生。ppar - α活化的这些作用伴随着心肌梗死面积的减小和血清肌酸激酶活性的降低。因此,非诺贝特在心肌缺血中的新保护作用的一部分是对RAS非经典轴的调节。
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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Nonclassical Axis of the Renin-Angiotensin System and Neprilysin: Key Mediators That Underlie the Cardioprotective Effect of PPAR-Alpha Activation during Myocardial Ischemia in a Metabolic Syndrome Model.

The activation of the renin-angiotensin system (RAS) participates in the development of metabolic syndrome (MetS) and in heart failure. PPAR-alpha activation by fenofibrate reverts some of the effects caused by these pathologies. Recently, nonclassical RAS components have been implicated in the pathogenesis of hypertension and myocardial dysfunction; however, their cardiac functions are still controversial. We evaluated if the nonclassical RAS signaling pathways, directed by angiotensin III and angiotensin-(1-7), are involved in the cardioprotective effect of fenofibrate during ischemia in MetS rats. Control (CT) and MetS rats were divided into the following groups: (a) sham, (b) vehicle-treated myocardial infarction (MI-V), and (c) fenofibrate-treated myocardial infarction (MI-F). Angiotensin III and angiotensin IV levels and insulin increased the aminopeptidase (IRAP) expression and decreased the angiotensin-converting enzyme 2 (ACE2) expression in the hearts from MetS rats. Ischemia activated the angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin receptor 1 (AT1R) and angiotensin III/angiotensin IV/angiotensin receptor 4 (AT4R)-IRAP axes. Fenofibrate treatment prevented the damage due to ischemia in MetS rats by favoring the angiotensin-(1-7)/angiotensin receptor 2 (AT2R) axis and inhibiting the angiotensin III/angiotensin IV/AT4R-IRAP signaling pathway. Additionally, fenofibrate downregulated neprilysin expression and increased bradykinin production. These effects of PPAR-alpha activation were accompanied by a reduction in the size of the myocardial infarct and in the activity of serum creatine kinase. Thus, the regulation of the nonclassical axis of RAS forms part of a novel protective effect of fenofibrate in myocardial ischemia.

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来源期刊
PPAR Research
PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.20
自引率
3.40%
发文量
17
审稿时长
12 months
期刊介绍: PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.
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