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体育训练与培哚普利治疗对自发性高血压大鼠动脉僵硬的影响:蛋白质组学分析及可能机制

Physical Training vs. Perindopril Treatment on Arterial Stiffening of Spontaneously Hypertensive Rats: A Proteomic Analysis and Possible Mechanisms.

作者信息

Miotto Danyelle Siqueira, Duchatsch Francine, Dionizio Aline, Buzalaf Marília Afonso Rabelo, Amaral Sandra Lia

机构信息

Joint Graduate Program in Physiological Sciences (PIPGCF), Federal University of Sao Carlos and São Paulo State University, UFSCar/UNESP, São Carlos 14801-903, Brazil.

Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo-USP, Bauru 17012-901, Brazil.

出版信息

Biomedicines. 2023 May 6;11(5):1381. doi: 10.3390/biomedicines11051381.

Abstract

(1) Background: Arterial stiffness is an important predictor of cardiovascular events. Perindopril and physical exercise are important in controlling hypertension and arterial stiffness, but the mechanisms are unclear. (2) Methods: Thirty-two spontaneously hypertensive rats (SHR) were evaluated for eight weeks: SHR (sedentary); SHR (sedentary treated with perindopril-3 mg/kg) and SHR (trained). Pulse wave velocity (PWV) analysis was performed, and the aorta was collected for proteomic analysis. (3) Results: Both treatments determined a similar reduction in PWV (-33% for SHR and -23% for SHR) vs. SHR, as well as in BP. Among the altered proteins, the proteomic analysis identified an upregulation of the EH domain-containing 2 (EHD2) protein in the SHR group, required for nitric oxide-dependent vessel relaxation. The SHR group showed downregulation of collagen-1 (COL1). Accordingly, SHR showed an increase (+69%) in the e-NOS protein level and SHR showed a lower COL1 protein level (-46%) compared with SHR. (4) Conclusions: Both perindopril and aerobic training reduced arterial stiffness in SHR; however, the results suggest that the mechanisms can be distinct. While treatment with perindopril increased EHD2, a protein involved in vessel relaxation, aerobic training decreased COL1 protein level, an important protein of the extracellular matrix (ECM) that normally enhances vessel rigidity.

摘要

(1) 背景:动脉僵硬度是心血管事件的重要预测指标。培哚普利和体育锻炼在控制高血压和动脉僵硬度方面很重要,但机制尚不清楚。(2) 方法:对32只自发性高血压大鼠(SHR)进行了为期8周的评估:SHR(久坐不动);SHR(久坐不动,接受3 mg/kg培哚普利治疗)和SHR(训练组)。进行脉搏波速度(PWV)分析,并收集主动脉进行蛋白质组学分析。(3) 结果:与SHR相比,两种治疗方法均使PWV有相似程度的降低(SHR降低33%,SHR降低23%),血压也降低。在发生改变的蛋白质中,蛋白质组学分析发现SHR组中含EH结构域蛋白2(EHD2)上调,该蛋白是一氧化氮依赖性血管舒张所必需的。SHR组胶原蛋白-1(COL1)下调。因此,与SHR相比,SHR的内皮型一氧化氮合酶(e-NOS)蛋白水平升高(+69%),SHR的COL1蛋白水平降低(-46%)。(4) 结论:培哚普利和有氧训练均降低了SHR的动脉僵硬度;然而,结果表明其机制可能不同。培哚普利治疗增加了参与血管舒张的EHD2蛋白,而有氧训练降低了COL1蛋白水平,COL1是细胞外基质(ECM)的一种重要蛋白,通常会增强血管硬度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c5/10216057/8ad1eb065d04/biomedicines-11-01381-g001.jpg

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