The KPs (kisspeptins) are a family of multifunctional peptides with established roles in cancer metastasis, puberty and vasoconstriction. The effects of KPs on endothelial cells have yet to be determined. The aim of the present study was to investigate the effects of KP-10 on endothelial cell growth and the mechanisms underlying those effects. The administration of recombinant KP-10 into the hindlimbs of rats with ischaemia significantly impaired blood flow recovery, as shown by laser Doppler, and capillary growth, as shown using histology, compared with the controls. HUVECs (human umbilical vein endothelial cells) express the KP receptor and were treated with KP-10 in culture studies. KP-10 inhibited endothelial cell tube formation and proliferation in a significant and dose-dependent manner. The HUVECs treated with KP exhibited the senescent phenotype, as determined using a senescence-associated β-galactosidase assay, cell morphology analysis, and decreased Sirt1 (sirtuin 1) expression and increased p53 expression shown by Western blot analysis. Intriguingly, a pharmacological Rho kinase inhibitor, Y-27632, was found to increase the proliferation of HUVECs and to reduce the number of senescent phenotype cells affected by KP-10. In conclusion, KP-10 suppressed endothelial cells growth both in vivo and in vitro in the present study. The adverse effect of KP on endothelial cells was attributable, at least in part, to the induction of cellular senescence.
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Research Article|
March 10 2014
Kisspeptin-10 induces endothelial cellular senescence and impaired endothelial cell growth
Sayaka Usui;
Sayaka Usui
*Division of Cardiology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama City, Kanagawa 227-8501, Japan
†Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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Yoshitaka Iso;
*Division of Cardiology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama City, Kanagawa 227-8501, Japan
‡Division of Cardiology, Showa University Fujigaoka Rehabilitation Hospital, 2-1-1 Fujigaoka, Yokohama City, Kanagawa 227-8518, Japan
Correspondence: Associate Professor Yoshitaka Iso (email ytkiso@hotmail.com).
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Masahiro Sasai;
Masahiro Sasai
*Division of Cardiology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama City, Kanagawa 227-8501, Japan
†Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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Takuya Mizukami;
Takuya Mizukami
*Division of Cardiology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama City, Kanagawa 227-8501, Japan
†Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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Hiroyoshi Mori;
Hiroyoshi Mori
*Division of Cardiology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama City, Kanagawa 227-8501, Japan
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Takuya Watanabe;
Takuya Watanabe
§Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
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Seiji Shioda;
Seiji Shioda
†Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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Hiroshi Suzuki
Hiroshi Suzuki
*Division of Cardiology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama City, Kanagawa 227-8501, Japan
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Publisher: Portland Press Ltd
Received:
August 19 2013
Revision Received:
January 06 2014
Accepted:
January 10 2014
Accepted Manuscript online:
January 10 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 127 (1): 47–55.
Article history
Received:
August 19 2013
Revision Received:
January 06 2014
Accepted:
January 10 2014
Accepted Manuscript online:
January 10 2014
Citation
Sayaka Usui, Yoshitaka Iso, Masahiro Sasai, Takuya Mizukami, Hiroyoshi Mori, Takuya Watanabe, Seiji Shioda, Hiroshi Suzuki; Kisspeptin-10 induces endothelial cellular senescence and impaired endothelial cell growth. Clin Sci (Lond) 1 July 2014; 127 (1): 47–55. doi: https://doi.org/10.1042/CS20130505
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