ID 113751
Title Alternative
Bilirubin action on angiogenesis
Author
Hamano, Hirofumi Tokushima University
Satoh, Akiho Tokushima University
Keywords
bilirubin
angiogenesis
endothelial cells
eNOS
Content Type
Journal Article
Description
Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as anti-oxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthesis (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner.
Journal Title
Hypertension Research
ISSN
13484214
09169636
NCID
AA10847079
Publisher
Springer Nature|The Japanese Society of Hypertension
Volume
38
Issue
11
Start Page
733
End Page
740
Published Date
2015-07-02
Remark
This is the Author's Accepted Manuscript of the following article: Bilirubin exerts pro-angiogenic property through Akt-eNOS-dependent pathway, Yasumasa Ikeda, Hirofumi Hamano, Akiho Satoh, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Ken-ichi Aihara, Koichiro Tsuchiya & Toshiaki Tamaki, Hypertension Research 38, 733-740 (2015), which has been published in final form at https://doi.org/10.1038/hr.2015.74.
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language
eng
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departments
Medical Sciences
Pharmaceutical Sciences