Role of matrix metalloproteinases and their tissue inhibitors as potential biomarkers of left ventricular remodelling in the athlete’s heart

The aim of the present study was to verify whether plasma MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitors of MMPs) could be used as potential markers of paraphysiological remodelling in the athlete’s heart, and to correlate these matrix parameters with echocardiographic signs of LV (left ventricular) remodelling. Plasma MMP-2 and MMP-9 were measured by zymography, and TIMP-1 and TIMP-2 were measured by ELISA in 42 veteran marathoners with AH (athlete’s heart), and in 25 sedentary healthy subjects (CTL). All subjects were submitted to a clinical examination and two-dimensional colour Doppler echocardiography together with the measurement of circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide); GGT (γ-glutamyl transpeptidase) was evaluated as a marker of cardiovascular disease. Veteran athletes had a significant elevation in LV dimensions and calculated LV mass index. Diastolic and systolic functions were normal for both groups. MMP-9 levels were significantly lower in AH than in CTL subjects (56.9±4.3 compared with 119.4±21.5 m-units/l, P<0.01). There were significant differences in MMP-2 between the two groups, with a down-regulation in the AH subjects (182.5±16.8~units/ml in CTL compared with 117.1±9.1~units/ml in AH, P<0.01). MMP-2 and MMP-2/TIMP-2 were inversely correlated with myocardial indices of hypertrophy in AH and CTL subjects. AH and CTL subjects showed similar TIMP values. The results of the present study indicate that MMPs and TIMPs could represent potential biomarkers of adaptive heart remodelling in the athletes. In addition, the inverse correlation of the MMP-2/TIMP-2 system with echocardiographic signs of myocardial hypertrophy could represent a new diagnostic and prognostic indicator useful in the evaluation of cardiovascular risk in athletes. Abbreviations: A, late diastolic peak velocity; AH, athlete’s heart; CTL, control; E, early diastolic peak velocity; ECM, extracellular matrix; EF, ejection fraction; GGT, γ-glutamyl transpeptidase; HF, heart failure; LV, left ventricular; LVEDD, LV end-diastolic diameter; LVM, LV mass; MMP, matrix metalloproteinase; NT-proBNP, N-terminal pro-B-type natriuretic peptide; TIMP, tissue inhibitor of MMP