Observational studies and inhibition studies indicate that matrix metalloproteinases (MMPs) participate in the left ventricular remodeling process. The Lee laboratory has demonstrated that broad spectrum MMP inhibition in mice attenuates ventricular dilation following myocardial infarction. However, the roles of specific MMPs in mediating this process are unclear. MMP-9, also known as gelatinase B or 92kDa gelatinase, is an MMP that is prominently overexpressed following acute myocardial infarction. A transgenic mouse with targeted deletion of the MMP-9 gene will be used to examine three Specific Aims highly relevant to the development of congestive heart failure following MI.
The Specific Aims of this proposal are. 1 . Explore the effects of targeted deletion of the MMP-9 gene on LV remodeling following experimental myocardial infarction. 2. Explore the effects of targeted deletion of the MMP-9 gene on LV hemodynamics following experimental myocardial infarction. 3. Explore the role of MMP-9 in localizing neutrophil infiltration and contributing to LV remodeling following ischemia/reperfusion.