Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in obese children and adolescents

Abstract

Matrix metalloproteinases (MMPs) have been implicated in the atherosclerotic process and risk factors for the disease such as hypertension, hyperlipidemia, or diabetes mellitus in adults. So far, circulating levels of MMPs and their tissue inhibitors (TIMPs) have not been assessed in children and adolescents with obesity, a known risk factor for cardiovascular disease. Plasma levels of MMP-9 and TIMP-1 were measured immunoenzymatically in 45 obese children and adolescents, aged 15 ± 1.8 years. The control group consisted of 28 healthy children, aged 14.5 ± 2.5 years. MMP-9 and TIMP-1 concentrations were higher in obese children than in the control group (MMP-9: 553.5 ± 311 vs 400.4 ± 204 ng/mL, respectively; P = .02; TIMP-1: 161.2 ± 32 vs 143.1 ± 20.1 ng/mL, respectively; P = .03). We found significantly higher levels of MMP-9 in obese children with coexisting hypertension than in obese normotensive patients (635 ± 308 vs 450 ± 289 ng/mL, respectively; P = .04). MMP-9 correlated with body mass index (BMI) ( r = 0.33, P = .005) and fasting insulin ( r = 0.3, P = .013); TIMP-1 correlated with BMI ( r = 0.35, P = .006). In the group of obese hypertensive children (n = 25), MMP-9 correlated with BMI ( r = 0.41, P = .001), systolic blood pressure ( r = 0.41, P = .002), fasting insulin ( r = 0.37, P = .006), and homeostasis model assessment index of insulin resistance ( r = 0.27, P = .03). TIMP-1 correlated with BMI ( r = 0.33, P = .025) and systolic ( r = 0.38, P = .008) and diastolic ( r = 0.47, P = .001) blood pressure. In the regression models, MMP-9 was found to be dependent on fasting insulin ( R 2 = 0.16, P = .04), and TIMP-1 on BMI ( R 2 = 0.14, P = .04). In the obese hypertensive group, TIMP-1 was dependent on diastolic blood pressure ( R 2 = 0.18, P = .04). Obese children and adolescents have elevated plasma concentrations of MMP-9 and TIMP-1. Coexistence of hypertension may exacerbate alterations of extracellular matrix turnover in these patients. It might be hypothesized that elevated MMP and TIMP concentrations may be related to increased cardiovascular risk in obese and particularly in obese hypertensive children and adolescents.