Methylglyoxal Induces Stem Cell Dysfunction Through Impaired Matrix Interactions After Myocardial Infarction

Background: Advanced glycation end-products (AGEs) have been associated with poorer outcomes in heart failure (HF) after myocardial infarction (MI). The contribution of AGEs to post-MI injury has yet to be shown. Methylglyoxal (MG) is considered the most important AGE precursor. To elucidate the role of MG in post-MI repair, this study used a mouse model that over-expresses the MG-metabolizing enzyme glyoxalase-1 (GLO1). Methods/Results: MI was induced in GLO1 over-expressing mice and their wild-type (WT) littermates. MI resulted in increased MG levels in hearts of both mouse groups. Left ventricular ejection fraction was superior in GLO1 mice (46.0±3.3%) compared to WT (33.9±1.8%, p=0.008) at 4 weeks post-MI. GLO1 mice also had smaller infarcts (41.5±2.2% vs. 57.3±7.1%, p=0.05) and improved chamber volumes. Immunohistochemistry at 4 weeks post-MI revealed greater arteriole (p=0.006) and capillary (p=0.03) density in GLO1 vs. WT mice, and an overall reduction in cardiomyocyte death through apoptosis (p=0....