Evaluation of plasma MMP-8, MMP-9 and TIMP-1 identifies candidate cardiometabolic risk marker in metabolic syndrome: results from double-blinded nested case–control study

• Published in: Metabolism, clinical and experimental clinical and experimental, 2015-04, Vol.64 (4), p.527-538
• Main Authors: Hoseini, Seyed Mehdi, Kalantari, Ali, Afarideh, Mohsen, Noshad, Sina, Behdadnia, Aram, Nakhjavani, Manouchehr, Esteghamati, Alireza
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers - blood; Cardiometabolic risk; Cardiovascular Diseases - blood; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - etiology; Case-Control Studies; Double-Blind Method; Endocrinology & Metabolism; Female; Humans; Inflammatory markers; Male; Matrix metalloproteinase; Matrix Metalloproteinase 8 - blood; Matrix Metalloproteinase 9 - blood; Metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - diagnosis; Metabolic Syndrome - epidemiology; Metabolic Syndrome - etiology; Middle Aged; Risk Factors; Tissue Inhibitor of Metalloproteinase-1 - blood; Tissue inhibitors of metalloproteinases; Young Adult
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2014.12.009

Abstract Aims 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). Conclusion 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.