Tissue Inhibitor of Matrix Metalloproteinase- 1 Is a Marker of Left Ventricular Diastolic Dysfunction in Diabetic Heart Disease

Background: Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) are regulators of extracellular matrix (ECM). Diabetes Mellitus (DM) is associated with abnormal cardiac ECM composition, which may contribute to the high incidence of myocardial dysfunction (typically diastolic dysfunction). We hypothesised that plasma MMP-9, TIMP1 & -2, by regulating the ECM, are related to diastolic dysfunction in patients with DM. Methods: Venous blood was obtained from 56 treated type-2 diabetics, and 16 age comparable controls. Circulating MMP-9, TIMP-I & -2 were measured by ELISA. Early (E) diastolic mitral inflow velocity was measured with pulse wave Doppler and early mitral annular velocity (E’), a recognised index of diastolic relaxation, measured with tissue Doppler on transthoracic echocardiogram. Results: Patients with DM had lower E , higher W E ratio and higher TMP-I levels (Table). There was no significant difference between MMP-9 and TIMP-2 levels between patients and controls. E but not the ratio of W E correlated positively with TIMP-I ( rd .3 1. ~ 0 . 0 2 ) . There were no statistically significant correlations between TIMP-I and treated systolic blood pressure and HbAlc (p=NS). Conclusion: Lower E’ and higher WE’ suggest impaired diastolic relaxation and elevated left ventricular filling pressure respectively. The relationship between TIMP-I and E may reflect increased myocardial fibrosis and consequent diastolic dysfunction.