Angiogenic activity of sesamin through the activation of multiple signal pathways

作者：Chung Byung Hee; Lee Jung Joon; Kim Jong Dai; Jeoung Dooil; Lee Hansoo; Choe Jongseon; Ha Kwon Soo; Kwon Young Geun; Kim Young Myeong^*

来源：Biochemical and Biophysical Research Communications, 2010, 391(1): 254-260.

DOI：10.1016/j.bbrc.2009.11.045

• Sesamin
• Angiogenesis
• Endothelial cell
• Signal cascade
• Vascular inflammation

The natural product sesamin has been known to act as a potent antioxidant and prevent endothelial dysfunction. We here found that sesamin increased in vitro angiogenic processes, such as endothelial cell proliferation, migration, and tube formation, as well as neovascularization in an animal model This compound elicited the activation Of multiple angiogenic signal modulators, such as ERK Akt, endothelial nitric oxide synthase (eNOS), NO production, FAK, and p38 MAPK. but not Src. The MEK inhibitor PD98059 and the PI3K inhibitor Wortmannin specifically inhibited sesamin-induced activation of the ERK and Akt/eNOS pathways. These inhibitors reduced angiogenic events, with high specificity for MEK/ERK-dependent cell proliferation and migration and PI3K/Akt-mediated tube formation Moreover, inhibition of p38 MAPK effectively inhibited sesamin-induced cell migration The angiogenic activity of sesamin was not associated with VEGF expression. Furthermore, this compound did not induce vascular permeability and upregulated ICAM-1 and VCAM-1 expression, which are hallmarks Of Vascular inflammation These results suggest that sesamin stimulates angiogenesis in vitro and in vivo through the activation of MEK/ERK-, PI3K/Akt/eNOS-, p125(FAK)-, and p38 MAPK-dependent pathways, without increasing vascular inflammation, and may be used for treating ischemic diseases and tissue regeneration.

• 出版日期2010-1-1