Reply to Agkul

Abstract

chymase prevented fibrosis and maintained left ventricle function after left ventricular repair in a rat chronic myocardial infarction model. Heart failure is a chronic syndrome in which cardiac remodeling plays an important role in the pathogenesis; furthermore, cardiac mast cells may be one of the mainstays of pathologic mechanism according to the current studies [2,3]. Protein kinase C signaling is a relatively new signal transduction pathway of mast cell degradation which currently attracts attention. Palaniyandi and coworkers introduced protein kinase C inhibition to prevent cardiac mast cell degranulation without affecting mast cell density and they performed e V1-2 treatment for rat cardiac mast cell degranulation and decreased myocardial fibrosis [4]. Although Kanemitsu and co-workers underlined that inhibition of fibrosis established by cardiac chymase via transforming growth factor-b, our study also demonstrated that chymase, mediator of mast cell degranulation, related with myocardial fibrosis especially by basic-FGF [2]. These new findings and our previous studies [2—5] demonstrate that chymase-positive mast cells were associated with not only increased fibrosis but degradation of these cells may contribute in decreased cardiac inflammation and remodeling. One of my concerns about this excellent study by Kanemitsu is that he and his colleagues may be performing chronic chymase inhibition with oral medications, when according to previous studies, cardiac mast cells have several mediators as tryptase, 5-lipoxygenase, cytokins, histamin, serglycin, proteoglycans, carboxypeptidase. Chymase, tryptase and carboxypeptidase are also known as mast cell-specific proteases. Recent studies show promising progress of mast cell specific proteases, so how can Kenemitsu help us by reducing fibrosis by only preventing onemast— cell specific protease, instead of directmast cells inhibition?