Abstract 3332: Homing of Cardiac Mast Cells Contributes to Myocardial Fibrosis and Diastolic Heart Failure in Mice With Sustained Inflammatory Signaling
Background: Transgenic mice with cardiac restricted overexpression of tumor necrosis factor (MHCsTNF mice) have increased myocardial fibrosis and diastolic dysfunction. Noting that mast cells accumulate in areas of ongoing tissue fibrosis, we asked whether increased mast cell homing was responsible for diastolic heart failure in the MHCTNF mice.
Results: Mast cell number increased 2–3-fold (p<0.01) in MHCsTNF mice compared to littermate (LM) controls. To determine the functional significance of mast cell homing we crossed the MHCsTNF mice with mast cell deficient (MC−/−) mice, and examined histology and diastolic function in the hearts from littermate (LM) controls, MHCsTNF, and MHCsTNF mast cell deficient (MC−/−/MHCsTNF). There was a significant 11-fold increase (p< 0.0001) in collagen volume fraction in MHCsTNF mice vs. LM controls, that was abrogated in the MC−/−/MHCsTNFmice. LV pressure-volume (PV) analyses of Langendorff perfused hearts showed that the PV curve was shifted leftward (p< 0.05) in the MHCsTNF mice, and that this leftward shift was normalized in the MC−/−/MHCsTNF mouse hearts (Figure⇓).
Conclusion: Taken together, these results suggest that increased mast cells homing to sites of inflammation can trigger progressive myocardial fibrosis and worsening LV diastolic function, suggesting that strategies that disrupt mast cells homing in inflammatory cardiomyopathies may prevent progressive LV dysfunction.