Temporal plasma profiles of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in patients with left ventricular hypertrophy

The structure of the myocardial matrix is dependent on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). LV remodeling in left ventricular hypertrophy (LVH) involves changes in the matrix which is mediated by the MMP/TIMP system. The central hypothesis of this study was that a specific MMP/TIMP plasma profile occurs in LVH. Left ventricular (LV) echocardiography was performed in 58 LVH patients (Age: 61 ± 2 years; systolic blood pressure: 139±3 mmHg) and 42 controls with no evidence of cardiovascular disease (Age: 52 ± 2; systolic blood pressure: 124±mmHg). Plasma was collected and MMP-2, -9, -13 and TIMP-1 and -2 levels were quantified by high sensitivity enzyme linked immunoassay (ELISA). LVH patients were serially measured at baseline, 6 and 12 months while control values one baseline timepoint. Despite blood pressure control to JNC VII guideline, LV mass remained elevated in LVH patients through the 12 month follow-up period. Additionally, LVH patients had elevated TIMP-1 and TIMP-2 levels and were less likely to have detectable levels of MMP-13. After 12 months of follow-up, LVH patients demonstrated persistent hypertrophy and a specific temporal profile of MMPs and TIMP. Notably, the greater than 50% reduction in detectable MMP-13 (detectable in 40% of controls vs. 11% of LVH at 12 months, p<0.05) indicate that MMP-13 may be a useful diagnostic/prognostic indicator in LVH. In addition, these abnormalities in the MMP/TIMP system, coupled with the presence of continued LVH, indicate that conventional medical management and achievement of blood pressure control failed to modify the MMP/TIMP profile which is critical in modulation of the myocardial matrix structure. The unique and important findings in this longitudinal study demonstrate that indices of a profibrotic cascade in HTN persist over time and may impede regression of LVH.