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Background and Study Objectives:Mast cells (MC) are increased in numbers at atherosclerotic and various cardiovascular diseases. We found that stem cell factor (SCF), MC growth factor, and MC density were significantly increased in the heart of mice with encephalomyocarditis virus (EMCV) myocarditis. Furthermore, MC-deficient mice had less prominent histopathologic lesions of viral myocarditis than controls (7.6 ± 3.5%vs.29.3 ± 15.6% area for infiltration; P < 0.01;7.6 ± 3.5%vs.30.0 ± 17.2% area for necrosis; P < 0.01,n=10). In this study, MC were reconstituted to deficient mice, and the histopathology and gene expression of mouse MC protease (mMCP) and MMP-9 as markers of remodeling were examined in the hearts of MC-reconstituted mice with myocarditis. Methods and Results:MC were reconstituted in WBB6F1-KitW/KitW-v(W/W V) mice (which have a mutation of c-kit, SCF receptor) by transplantation of bone marrow-derived MCc-kit+. MC-reconstituted W/WVmice was then inoculated with 10 pfu of EMCV i.p. On day7, myocardial necrosis and cellular infiltration were more prominent in reconstituted than in non-reconstituted mice (W/WVmice:15.9 ± 5.0%vs.8.2 ± 4.9% area for infiltration; P < 0.01,6.9 ± 3.7%vs.4.1 ± 1.6% area for necrosis; P < 0.05, n=10). The gene expressions of mMCP-4,-5 (MC chymase) and MMP-9 were higher in the reconstituted W/WVmice than in control W/WVmice. Furthermore, the gene expressions of mMCP-4,-5 and MMP-9 were correlated. Conclusions:In viral myocarditis, MC exert deleterious effects. The fibrogenic process that they mediate begins in the acute phase of disease, and inhibition of their activation may be therapeutic.