Tryptophan metabolite 5-methoxytryptophan ameliorates arterial denudation-induced intimal hyperplasia via opposing effects on vascular endothelial and smooth muscle cells

Chung Huang Chen, Yen Chun Ho, Hua Hui Ho, Li Yu Liang, Wei Cheng Jiang, Guan Lin Lee, Jen Kuang Lee, Yu Juei Hsu, Cheng Chin Kuo, Kenneth K. Wu, Shaw Fang Yet*

*此作品的通信作者

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses. This study aimed to investigate the function and mechanisms of 5-MTP in interventional procedure-induced restenosis. We found that after mouse femoral artery denudation with a guide wire, 5-MTP accelerated recovery of endothelium in the denuded area and reduced vascular leakage and intimal thickening. 5-MTP increased endothelial cell proliferation in the denuded arteries and rescued TNF-α-reduced endothelial cell proliferation and migration, likely via maintaining vascular endothelial growth factor receptor 2 activation. In contrast, 5-MTP preserved differentiated phenotype of medial vascular smooth muscle cells (VSMCs) and decreased VSMC proliferation and migration. Furthermore, 5-MTP maintained expression levels of critical transcription factors for VSMC marker gene expressions via attenuated activation of p38 MAPK and NFκB-p65. Our findings uncover a novel protective mechanism of 5-MTP in restenosis. In response to denudation injury, 5-MTP attenuates intimal hyperplasia via concerted but opposing actions on endothelial cells and VSMCs. Taken together, our results suggest that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.

原文English
頁(從 - 到)8604-8622
頁數19
期刊Aging
11
發行號19
DOIs
出版狀態Published - 2019

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