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Eur J Cardiothorac Surg 2006;29:638
© 2006 Elsevier Science NL

Letter to the Editor

Reply to Akgul and Noon

Shinji Takai * , Toshihiko Ibaraki, Michiko Muramatsu, Mizuo Miyazaki

Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka 569-8686, Japan

Received 12 January 2006; accepted 16 January 2006.

* Corresponding author. Tel.: +81 726 84 7292; fax: +81 726 84 6518. (Email: pha010{at}art.osaka-med.ac.jp).

Key Words: Angiogenesis • Lung cancer • Chymase • Mast cells

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)-ß 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-ß is known to facilitate cardiac fibrosis, we also believe that chymase-positive mast cells facilitate cardiac fibrosis via TGF-ß activation [2].

However, in hamsters grafted with a sponge, chymase facilitated angiogenesis via angiotensin 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 chymase-positive mast cells surrounding tumors are closely involved with tumor growth by increasing interstitial cells and elevating angiogenesis.

References

  1. Akgul A, Skrabal CA, Thompson LO, Loebe M, Lafuente JA, Noon GP, Youker KA. Role of mast cells and their mediators in failing myocardium under mechanical ventricular support. J Heart Lung Transplant 2004;23:709.[CrossRef][Medline]
  2. Takai S, Jin D, Sakaguchi M, Katayama S, Muramatsu M, Sakaguchi M, Matsumura E, Kim S, Miyazaki M. A novel chymase inhibitor, 4-[1-([bis-(4-methyl-phenyl)-methyl]-carbamoyl)3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid (BCEAB), suppressed cardiac fibrosis in cardiomyopathic hamsters. J Pharmacol Exp Ther 2003;305:17.[Abstract/Free Full Text]
  3. Muramatsu M, Katada J, Hayashi I, Majima M. Chymase as a proangiogenic factor. A possible involvement of chymase-angiotensin-dependent pathway in the hamster sponge angiogenesis model. J Biol Chem 2000;275:5545.[Abstract/Free Full Text]




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