Angiogenic activity of bFGF and VEGF suppressed by proteolytic cleavage by neutrophil elastase |
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Authors: | Ai Shingo Cheng Xian Wu Inoue Aiko Nakamura Kae Okumura Kenji Iguchi Akihisa Murohara Toyoaki Kuzuya Masafumi |
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Affiliation: | a Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan b Department of Cardiovascular Research Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan c Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan d Branch of Medicine in Kohjin Hospital, 1-710 Shikenya, Moriyama ward, Nagoya, Japan e Department of Cardiology, College of Medical, Yanbian University, 119 Juzijie, Yanji, Jilin Province 133000, China |
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Abstract: | Neutrophil elastase (NE), a serine protease released from the azurophil granules of activated neutrophil, proteolytically cleaves multiple cytokines, and cell surface proteins. In the present study, we examined whether NE affects the biological abilities of angiogenic growth factors such as basic-fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). NE degraded bFGF and VEGF in a time- and concentration-dependent manner, and these degradations were suppressed by sivelestat, a synthetic inhibitor of NE. The bFGF- or VEGF-mediated proliferative activity of human umbilical vein endothelial cells was inhibited by NE, and the activity was recovered by sivelestat. Furthermore, NE reduced the bFGF- or VEGF-induced tubulogenic response of the mice aortas, ex vivo angiogenesis assay, and these effects were also recovered by sivelestat. Neutrophil-derived NE degraded potent angiogenic factors, resulting in loss of their angiogenic activity. These findings provide additional insight into the role played by neutrophils in the angiogenesis process at sites of inflammation. |
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Keywords: | Neutrophil elastase Sivelestat bFGF VEGF Degradation Angiogenesis |
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