0375: Re-evaluation of the role of mast cell in cardiac tissue following myocardial infarction

Inflammatory cells orchestrate post-ischemic cardiac remodeling after myocardial infarction (MI). Studies in Kit mutant mice suggest key roles for mast cells in post-ischemic tissue remodeling. However, Kit mutations affect multiple cell types of both immune and non-immune origin. The aim of this study was to address the impact of mast cells on cardiac function following MI, using selectively mast cell-deficient mice (Cpa3Cre/+ mice).The number of mast cell progenitor (Lin-CD45+CD34+FcγRII/III+β7+) increased in the bone marrow and the white adipose tissue on day 3 after MI, infiltrated the heart on day 5 and differentiated to mature mast cells (Cd117+FcεRI+Sca1+) by day 7 in cardiac tissue. To assess the functional effect of mast cell infiltration, the cardiac function 14 days following MI was assessed in wild-type (WT) and 3 mast cells deficient mice models, the kitW/Wv mice, the Cpa3Cre/+ mice and mice treated with the degranulation inhibitor DSCG (50 μg/g, once a day). There was a significant decrease of the left ventricular shortening fraction in all 3 mast cell deficient models compared to WT mice (1.4-, 1.6- and 2-fold respectively) that correlated with increased cardiomyocyte apoptosis in the kitW/Wv mice; and increased fibrosis in the DSCG-treated mice (n=8-14 per group, p