Cardiac Overexpression of Membrane Type-1 Matrix Metalloproteinase Causes Left Ventricular Remodeling and Pump Dysfunction in Peripartum Cardiomyopathy

Introduction: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure (HF) in pregnancy. Like other forms of HF, left ventricular (LV) remodeling (LV dilation and LV pump dysfunction) occur with PPCM. The matrix metalloproteinases (MMPs) are implicated as a cause of adverse left ventricular (LV) remodeling and progression to HF. However, the role of MMPs in PPCM remains unclear. Within the class of membrane type MMPs, the subtype membrane type-1 MMP (MT1-MMP) is expressed in human myocardium and is known to be increased in HF. We tested the hypothesis that a causal relationship exists between myocardial overexpression of MT1-MMP and the development of PPCM. Methods/Results: Pregnant transgenic mice designed to overexpress MT1-MMP (MT1OE; n=8) in cardiomyocytes and littermate wild-type (WT; n=8) and corresponding non-pregnant controls (n=6 each group) were used. MT1-MMP activity was higher in the non-pregnant MT1OE mice than in WT mice and further differentially increased with pregnancy (Fig, pan...