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基质金属蛋白酶-2、-9与儿童及青少年动脉僵硬度:慢性肾脏病、糖尿病和高血压的作用

Matrix metalloproteinase -2, -9 and arterial stiffness in children and adolescents: The role of chronic kidney disease, diabetes, and hypertension.

作者信息

Stabouli Stella, Kotsis Vasilios, Maliachova Olga, Printza Nikoleta, Chainoglou Athanasia, Christoforidis Athanasios, Taparkou Anna, Dotis John, Farmaki Evangelia, Zafeiriou Dimitrios

机构信息

1st Department of Pediatrics, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece.

3rd Department of Internal Medicine, Aristotle University of Thessaloniki, Hypertension-24h ABPM Center, Papageorgiou General Hospital, Thessaloniki, Greece.

出版信息

Int J Cardiol Hypertens. 2020 Feb 6;4:100025. doi: 10.1016/j.ijchy.2020.100025. eCollection 2020 Mar.

DOI:10.1016/j.ijchy.2020.100025
PMID:33447754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7803037/
Abstract

BACKGROUND AND AIMS

Matrix metalloproteinases (MMPs) may contribute to the pathogenesis of arterial stiffness inducing extracellular matrix remodeling. We aimed to compare MMP-2 and -9 levels in children with chronic kidney disease (CKD), type 1 diabetes (without chronic kidney disease) and healthy control and to investigate associations of MMPs levels with cardiovascular risk factors and markers of arterial stiffness.

METHODS

The study population included 33 CKD, 18 type 1 diabetes patients, and 24 healthy controls. MMP-2, MMP-9, office blood pressure, pulse wave analysis, and carotid-femoral pulse wave velocity (cfPWV) measurements were performed.

RESULTS

MMP-2 levels were higher in the CKD compared to the diabetes and control groups (p < 0.05). MMP-9 levels did not differ among groups. In hypertensive individuals logMMP-2 independently associated with PWV z score (β = 0.744, 95%CI 0.105 to 2.921,  < 0.05) after adjustment for age, sex, GRF, and phosphate levels. Creatinine levels correlated positively with MMP-2 in the CKD (r = 0.39, p < 0.05) and negatively in the diabetes group (r = -0.72, p < 0.05). Cholesterol levels correlated with MMP-2 in the diabetes group (r = 0.70, p < 0.05). Phosphate levels correlated with MMP-2 level in the control group (r = 0.67, p < 0.05). In multivariate regression model adjusted for age and sex, including phosphate and GRF as covariates, only phosphate predicted logMMP-2 levels (β = 0.333, 95%CI 0.060 to 0.671,  < 0.05).

CONCLUSIONS

MMP-2 associated with arterial stiffness in the presence of hypertension, while the role of MMP-9 is less clear in children with CKD or type 1 diabetes. Whether up-regulation of MMPs could predict poor outcomes in young high-risk patient groups need to be confirmed by future studies.

摘要

背景与目的

基质金属蛋白酶(MMPs)可能通过诱导细胞外基质重塑而参与动脉僵硬度的发病机制。我们旨在比较慢性肾脏病(CKD)患儿、1型糖尿病(无慢性肾脏病)患儿及健康对照者的MMP - 2和MMP - 9水平,并研究MMPs水平与心血管危险因素及动脉僵硬度标志物之间的关联。

方法

研究人群包括33例CKD患儿、18例1型糖尿病患者及24例健康对照者。进行了MMP - 2、MMP - 9、诊室血压、脉搏波分析及颈股脉搏波速度(cfPWV)测量。

结果

与糖尿病组和对照组相比,CKD组的MMP - 2水平更高(p < 0.05)。各组间MMP - 9水平无差异。在高血压个体中,在调整年龄、性别、肾小球滤过率(GRF)和磷酸盐水平后,logMMP - 2与PWV z评分独立相关(β = 0.744,95%可信区间0.105至2.921,p < 0.05)。在CKD组中,肌酐水平与MMP - 2呈正相关(r = 0.39,p < 0.05),而在糖尿病组中呈负相关(r = -0.72,p < 0.05)。糖尿病组中胆固醇水平与MMP - 2相关(r = 0.70,p < 0.05)。对照组中磷酸盐水平与MMP - 2水平相关(r = 0.67,p < 0.05)。在调整年龄和性别的多变量回归模型中,将磷酸盐和GRF作为协变量纳入,只有磷酸盐可预测logMMP - 2水平(β = 0.333,95%可信区间0.060至0.671,p < 0.05)。

结论

在高血压情况下,MMP - 2与动脉僵硬度相关,而MMP - 9在CKD或1型糖尿病患儿中的作用尚不清楚。MMPs的上调是否能预测年轻高危患者群体的不良结局有待未来研究证实。

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