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基质金属蛋白酶和组织金属蛋白酶抑制剂水平与肥胖患者的人体测量参数、血压和内皮功能相关。

MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity.

机构信息

Faculty of Medicine of Sousse, Department of Physiology and Functional Exploration, University of Sousse, UR 12ES06, Sousse, Tunisia.

Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia.

出版信息

Sci Rep. 2021 Oct 8;11(1):20052. doi: 10.1038/s41598-021-99577-2.

Abstract

The association between matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs) and obesity as well as obesity-related disease including metabolic syndrome is not fully explored. Our aims are that: (i) to evaluate the plasma levels of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2 and their ratios in non-obese people, overweight and obese people with or without metabolic syndrome, (ii) to investigate correlations between MMPs or TIMPs levels and several anthropometric parameters, blood pressure, endothelial function. Anthropometric and biochemical parameters were determined in 479 randomly selected participants, subdividing according to body mass index (BMI) and metabolic syndrome status. Plasma MMPs and TIMPs levels were measured. The assessment of endothelial function was characterized in people with obesity, overweight and non-obese, using laser Doppler Flowmetry. Obese people have elevated MMP-1, MMP-2, TIMP-1, TIMP-2 levels and decreased MMP-3/TIMP-1 and MMP-9/TIMP-1 ratios compared with non-obese people. MMP-1 levels and MMP-1/TIMP-1 ratio were positively correlated with BMI and waist circumference (WC) while MMP-2 levels were negatively correlated with BMI and WC values in obese people. MMP-3 levels and MMP-3/TIMP-1 ratio were positively correlated with systolic blood pressure (SBP) or diastolic blood pressure (DBP) in obese and metabolic syndrome people. Additionally, MMP-9 levels and MMP-9/TIMP-1 ratio were negatively correlated with endothelium-dependent response in obese and metabolic syndrome people. MMP-1, MMP-2, TIMP-1, TIMP-2 levels were increased in obese subjects. Significant correlations between anthropometric parameters and MMP-1 as well as MMP-1/TIMP-1 ratio supported these results. MMP-3 and -9 levels as well as their ratios with TIMP-1 were associated with blood pressure and endothelial-dependent response, respectively. In conclusion, our results demonstrated that MMP-1, MMP-3 and MMP-9 levels were correlated with several obesity-related parameters including BMI, WC, blood pressure and endothelial-dependent response. Our findings will hopefully provide new aspects for the use of MMPs and TIMPs as clinical biomarkers in obesity-related cardiovascular diseases such as metabolic syndrome and hypertension. The lack of measure of MMPs activity in plasma and relevant organs/tissues in obesity and metabolic syndrome is considered as a limitation in this report.

摘要

基质金属蛋白酶(MMPs)、金属蛋白酶组织抑制剂(TIMPs)与肥胖以及肥胖相关疾病(如代谢综合征)之间的关系尚未完全阐明。我们的目的是:(i)评估非肥胖、超重和肥胖人群以及伴有或不伴有代谢综合征人群的血浆基质金属蛋白酶 1(MMP-1)、MMP-2、MMP-3、MMP-9、TIMP-1 和 TIMP-2 水平及其比值;(ii)探讨 MMPs 或 TIMPs 水平与多种人体测量学参数、血压、内皮功能之间的相关性。对 479 名随机选择的参与者进行了人体测量学和生化参数的测定,根据体重指数(BMI)和代谢综合征的状态进行了细分。测定了血浆 MMPs 和 TIMPs 水平。采用激光多普勒血流计评估肥胖、超重和非肥胖人群的内皮功能。与非肥胖者相比,肥胖者的 MMP-1、MMP-2、TIMP-1、TIMP-2 水平升高,MMP-3/TIMP-1 和 MMP-9/TIMP-1 比值降低。MMP-1 水平和 MMP-1/TIMP-1 比值与 BMI 和腰围(WC)呈正相关,而 MMP-2 水平与肥胖者的 BMI 和 WC 值呈负相关。MMP-3 水平和 MMP-3/TIMP-1 比值与肥胖和代谢综合征患者的收缩压(SBP)或舒张压(DBP)呈正相关。此外,MMP-9 水平和 MMP-9/TIMP-1 比值与肥胖和代谢综合征患者的内皮依赖性反应呈负相关。肥胖者的 MMP-1、MMP-2、TIMP-1、TIMP-2 水平升高。MMP-1 与 MMP-1/TIMP-1 比值与人体测量学参数之间存在显著相关性,支持了这些结果。MMP-3 和 MMP-9 水平及其与 TIMP-1 的比值分别与血压和内皮依赖性反应相关。总之,我们的研究结果表明,MMP-1、MMP-3 和 MMP-9 水平与 BMI、WC、血压和内皮依赖性反应等多种肥胖相关参数相关。我们的发现有望为 MMPs 和 TIMPs 作为肥胖相关心血管疾病(如代谢综合征和高血压)的临床生物标志物提供新的依据。本报告认为,在肥胖和代谢综合征中缺乏对 MMPs 活性在血浆和相关器官/组织中的测量是一个局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96c8/8501083/7126bfeb6d08/41598_2021_99577_Fig1_HTML.jpg

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