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. Dr. Shaw-Fang Yet from the Institute of Cellular and System Medicine investigated the function and mechanisms of 5-MTP in interventional procedure-induced restenosis and uncovered a novel protective mechanism of 5-MTP in restenosis, suggesting that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.
The team 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-alpha-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 NFkappaB-p65.
Citation: Chen CH, Ho YC, Ho HH, Liang LY, Jiang WC, Lee GL, Lee JK, Hsu YJ, Kuo CC, Wu KK, Yet, SF. Tryptophan metabolite 5-methoxytryptophan ameliorates arterial denudation-induced intimal hyperplasia via opposing effects on vascular endothelial and smooth muscle cells. Aging. 2019 Oct 9;11(19):8604-8622.