About one in four myocardial infarction (MI) patients progress to develop congestive heart failure, which
has a 5-year mortality rate of 50%. The goal of this project is to understand post-MI roles of matrix
metalloproteinase-12 (MMP-12) by establishing how MMP-12 serves as a resolution promoting factor to
stimulate the transition from inflammation to repair. We hypothesize that MMP-12 regulates individual
neutrophil, macrophage, and fibroblast physiology to promote the resolution of post-MI inflammation
and stimulate repair. Our specific aims will explore the mechanism whereby MMP-12 turns off pro-
inflammation (aim 1), initiates anti-inflammation (aim 2), and promotes repair (aim 3). Innovation lies in the
evaluation of MMP-12 post-MI to connect early cell functions to late remodeling outcomes and in the
integration of multi-discipline approaches to explore the mechanisms whereby MMP-12 regulates resolution.
This study will drive forward the understanding of the molecular basis of LV remodeling and will identify novel
intervention targets directed at MMP-12.