Reply to the Letter to the Editor Reply to Akgul and Noon

Chymase is a protease found in mast cell granules with a variety of enzymatic functions. Chymase converts angiotensin I to angiotensin II, which is closely involved with angiogenesis by activating vascular endothelial growth factors (VEGF) and matrix metalloproteases (MMP). As suggested by Akgul and Noon, chymase-positive mast cells may be closely involved with fibrosis of the heart [1]. We previously reported that chymase converted the precursor of transforming growth factor (TGF)-b to its active form in cultured fibroblasts [2]. In addition, using hamsters with myocardiopathy, we confirmed that the number of chymase-positive mast cells increased as cardiac fibrosis advanced and that chymase inhibitors suppressed cardiac fibrosis. Since TGF-b is known to facilitate cardiac fibrosis, we also believe that chymase-positive mast cells facilitate cardiac fibrosis via TGF-b activation [2]. However, in hamsters grafted with a sponge, chymase facilitated angiogenesis viaangiotensin II production [3]. Akgul and Noon suggested that, in general, angiogenesis and fibrosis are opposing phenomena. Tumor cells produce basic fibroblast growth factor (bFGF), which aids fibroblast proliferation and this factor is a potent angiogenesis promoter. We did not investigate fibrosis around tumors, but we believe that bFGF and VEGF that are released from interstitial cells around tumors are closely involved with facilitating angiogenesis. We therefore propose that chymase facilitates both fibroblast proliferation and angiogenesis and that chymasepositive mast cells surrounding tumors are closely involved with tumor growth by increasing interstitial cells and elevating angiogenesis.