Tissue inhibitors of matrix metalloproteinase as a prognostic biomarker of hypertrophic cardiomyopathy

Abstract

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitor of matrix metalloproteinases (MMPs). MMPs/TIMPs balance is well known to play important roles in myocardial remodelling regulation. TIMPs biological role suggests that an up-regulation leads to extracellular matrix accumulation, whereas a down-regulation results in an increased matrix proteolysis. TIMPs are also able to influence cardiomyocyte hypertrophy and/or hypertrophic remodelling of the myocardium. We aimed to determine whether circulating tissue inhibitor of MMPs (TIMP-1 and TIMP-2) could be a prognostic biomarker in patients with hypertrophic cardiomyopathy (HCM). Twenty-one HCM patients and twenty-two age-matched non-HCM (aged: 46 ± 14), plasma level of TIMP-1 and TIMP-2 were assayed by ELISA (Enzyme Linked Immuno Sorbent Assay ) Sandwich-type. To assess the predictive accuracy of biomarkers we performed the Receiver Operating Characteristic (ROC) curve analysis. The 95% confidence interval (CI) has been also calculated for sensitivity and specificity. Levels of TIMP-1 were significantly higher in HCM patients than non-HCM (62.50 ± 57.44 vs. 28.73 ± 11.70 ng/ml; P = 0.017). There was no significant difference for circulating TIMP-2 level. Higher TIMP-1 levels correlated negatively with left ventricular mass ( r = − 0.566; P = 0.018) and intraventricular septum thickness ( r = −0.604; P = 0.008). ROC curve analysis showed that plasma TIMP-1 achieved a good predicting performance of HCM with an area under curve (AUC): 0.733, 95% CI: 0.573−0.893, P = 0.013. The predictive value of TIMP-1 was > 47.5 ng/ml with a good specificity of 93.75% and a quite modest sensitivity 40%. Our findings do suggest that TIMP-1 may be a useful prognostic biomarker that could discriminate hypertrophic cardiomyopathy presence.