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Abstract：
OBJECTIVE: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are dysregulated in metabolic syndrome (MetS) and associated with atherosclerosis and cardiovascular disease (CVD). Previous studies on the association between MMPs/TIMPs and MetS are controversial. We aimed to evaluate circulating MMP-8, MMP-9 and TIMP-1 in a group of MetS individuals and healthy controls to find the potential marker associated with MetS and its components.
METHODS: 243 MetS individuals participated in a nested case-control design, of whom 63 were excluded (study subjects for analysis n=180; 87 MetS cases, 93 controls). We employed the International Diabetes Federation criteria using national waist circumference cutoffs for case definition. Anthropometric and biochemical measurements were done using standard methods.
RESULTS: Plasma MMP-8, TIMP-1, tumor necrosis factor-alpha (TNF-α), highly sensitive C-reactive protein (hs-CRP) and MMP-8/TIMP-1 ratio were significantly higher in MetS cases (P for all < 0.05). Each component of MetS except raised fasting plasma glucose positively correlated with MMP-8 and numbers of MetS components increased with higher MMP-8. In all regression models, MMP-8 was a significant predictor of MetS and in the final model the relationship persisted even after adjusting for pro-inflammatory cytokines hs-CRP and TNF-α (odds ratio=6.008, 95% confidence interval: 1.612-22.389, P=0.008).
CONCLUSIONS: Strong associations of MMP-8 with components of MetS in univariate, bivariate and multivariate models suggest plasma MMP-8 as a potential cardiometabolic risk marker for MetS. Higher MMP-8 in MetS is possibly mediated through mechanisms both dependent and independent of chronic low grade inflammation.
METHODS: 243 MetS individuals participated in a nested case-control design, of whom 63 were excluded (study subjects for analysis n=180; 87 MetS cases, 93 controls). We employed the International Diabetes Federation criteria using national waist circumference cutoffs for case definition. Anthropometric and biochemical measurements were done using standard methods.
RESULTS: Plasma MMP-8, TIMP-1, tumor necrosis factor-alpha (TNF-α), highly sensitive C-reactive protein (hs-CRP) and MMP-8/TIMP-1 ratio were significantly higher in MetS cases (P for all < 0.05). Each component of MetS except raised fasting plasma glucose positively correlated with MMP-8 and numbers of MetS components increased with higher MMP-8. In all regression models, MMP-8 was a significant predictor of MetS and in the final model the relationship persisted even after adjusting for pro-inflammatory cytokines hs-CRP and TNF-α (odds ratio=6.008, 95% confidence interval: 1.612-22.389, P=0.008).
CONCLUSIONS: Strong associations of MMP-8 with components of MetS in univariate, bivariate and multivariate models suggest plasma MMP-8 as a potential cardiometabolic risk marker for MetS. Higher MMP-8 in MetS is possibly mediated through mechanisms both dependent and independent of chronic low grade inflammation.
摘要：
目的：基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs）在代谢综合征（MetS）中失调，并与动脉粥样硬化和心血管疾病（CVD）有关。先前关于MMPs/TIMPs与MetS之间关联的研究存在争议。我们旨在评估一组MetS个体和健康对照中的循环MMP-8，MMP-9和TIMP-1，以寻找与MetS及其组分相关的潜在标志物。
方法：243名MetS个人参与了嵌套病例对照设计，其中63例被排除在外(用于分析的研究对象n=180；87例MetS病例，93个控件）。我们采用国际糖尿病联合会标准，使用国家腰围截止值作为病例定义。使用标准方法进行人体测量和生化测量。
结果：血浆MMP-8，TIMP-1，肿瘤坏死因子-α（TNF-α），高敏C反应蛋白(hs-CRP)和MMP-8/TIMP-1比值明显高于MetS患者(P均<0.05)。除空腹血糖升高外，MetS的每个成分均与MMP-8呈正相关，并且随着MMP-8的升高，MetS成分的数量增加。在所有回归模型中，MMP-8是MetS的重要预测因子，在最终模型中，即使在调整促炎细胞因子hs-CRP和TNF-α后，这种关系仍然存在（比值比=6.008，95％置信区间：1.612-22.389，P=0.008）。
结论：单变量中MMP-8与MetS成分的强关联，双变量和多变量模型提示血浆MMP-8是MetS的潜在心脏代谢风险标志物.MetS中更高的MMP-8可能是通过依赖和独立于慢性低度炎症的机制介导的。
方法：243名MetS个人参与了嵌套病例对照设计，其中63例被排除在外(用于分析的研究对象n=180；87例MetS病例，93个控件）。我们采用国际糖尿病联合会标准，使用国家腰围截止值作为病例定义。使用标准方法进行人体测量和生化测量。
结果：血浆MMP-8，TIMP-1，肿瘤坏死因子-α（TNF-α），高敏C反应蛋白(hs-CRP)和MMP-8/TIMP-1比值明显高于MetS患者(P均<0.05)。除空腹血糖升高外，MetS的每个成分均与MMP-8呈正相关，并且随着MMP-8的升高，MetS成分的数量增加。在所有回归模型中，MMP-8是MetS的重要预测因子，在最终模型中，即使在调整促炎细胞因子hs-CRP和TNF-α后，这种关系仍然存在（比值比=6.008，95％置信区间：1.612-22.389，P=0.008）。
结论：单变量中MMP-8与MetS成分的强关联，双变量和多变量模型提示血浆MMP-8是MetS的潜在心脏代谢风险标志物.MetS中更高的MMP-8可能是通过依赖和独立于慢性低度炎症的机制介导的。
