Abstract
Introduction: Diastolic recoil is an important component of cardiac relaxation and depends on the efficient recovery of energy stored in cardiac tissue during systolic deformation. Abnormalities in the cardiac extracellular matrix (ECM) have been implicated in cardiovascular remodeling and diastolic dysfunction. Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs) regulate protein deposition and degradation in the ECM. We compared MMP and TIMP profiles in healthy seniors to study the role of ECM turnover in diastolic recoil efficiency. Hypothesis: Increased levels of MMPs and TIMPs involved in ECM protein turnover will be associated with improved diastolic recoil efficiency. Methods: Healthy but sedentary seniors (13 men, 9 women; age 68 ± 8 yrs) underwent echocardiogram and plasma biomarker assay for human MMP 1, 2, 3, 7, 9 and TIMP 1, 2, 3, 4. Diastolic recoil efficiency was modeled as an elastic spring and measured as the ratio of systolic longitudinal excursion (Sexc) and early diastolic excursion (EDexc) obtained from tissue doppler velocity-time integrals. Results: Increasing EDexc/Sexc ratios were directly associated with TIMP-1 levels (R=0.45, p=0.035) and TIMP-4 levels (R=0.50, p=0.019). There was a trend towards an association with MMP-2 (R=0.76, p=0.076). There were no significant correlations between the EDexc/Sex ratio and MMPs 1, 3, 7 or 9, TIMPs 2 or 3, MMP2/TIMP1, MMP2/TIMP4, MMP9/TIMP1, or MMP9/TIMP4 ratios. Conclusions: Abnormalities in ECM deposition and degradation via MMPs and TIMPs may impact cardiac relaxation by altering the efficiency of energy recovery in the transition from systole to diastole. TIMP-1 and -4 may preserve diastolic efficiency by attenuating fibrillar collagen fragmentation and pathologic remodeling of the ECM. MMP-2 trended towards a positive association with diastolic recoil efficiency and likely mediates a beneficial effect outside of its proteolytic action.
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