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

ABSTRACT: 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-?-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 NF?B-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.

SUBMITTER: Chen CH

PROVIDER: S-EPMC6814618 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Chen Chung-Huang CH Ho Yen-Chun YC Ho Hua-Hui HH Liang Li-Yu LY Jiang Wei-Cheng WC Lee Guan-Lin GL Lee Jen-Kuang JK Hsu Yu-Juei YJ Kuo Cheng-Chin CC Wu Kenneth K KK Yet Shaw-Fang SF

Aging 20191009 19

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 ...[more]

PMID: 31596731

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Project description:BACKGROUND AND OBJECTIVES:Preoperative arterial function is associated with arteriovenous fistula (AVF) development. Because arterial pathology may correlate with its function, preexisting arterial intimal hyperplasia may be associated with AVF development. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Vascular specimens obtained from 125 patients (with minimal 2 mm arterial diameter and 2.5 mm venous diameter) undergoing AVF creation were quantified for arterial intimal hyperplasia, arterial medial fibrosis, arterial microcalcification, and venous intimal hyperplasia. A 6-week postoperative ultrasound quantified AVF diameter, blood flow, and stenosis. Clinical AVF maturation was assessed using a predefined protocol. In a prospective cohort study design, we investigated the association of preexisting arterial intimal hyperplasia with the postoperative AVF diameter, blood flow, stenosis, and clinical maturation failure, after controlling for baseline demographics, comorbidities, and preoperative vein diameter. Additional analyses evaluated whether other vascular pathologies interacted with arterial intimal hyperplasia in affecting AVF outcomes. RESULTS:The median intimal thickness of the native artery was 22.0 μm (interquartile range, 14.8-37.1 μm). The median postoperative AVF diameter was 4.8 (interquartile range, 3.7-6.8) mm, blood flow was 796 (interquartile range, 413-1036) ml/min, and stenosis was present in 37 out of 98 patients with ultrasound data (38%). AVF nonmaturation occurred in 37 out of 125 patients (30%). Preexisting arterial intimal thickness was not significantly associated with AVF blood flow (-12 ml/min; 95% confidence interval [95% CI], -55 to 30 ml/min), diameter (-0.04 mm; 95% CI, -0.21 to 0.14 mm), stenosis (odds ratio, 0.93; 95% CI, 0.75 to 1.14), or clinical maturation failure (odds ratio, 1.07; 95% CI, 0.90 to 1.28), all per 10 μm increase. There was no significant interaction of preexisting arterial intimal thickness and postoperative AVF outcomes with arterial medial fibrosis, arterial microcalcification, or venous intimal hyperplasia. CONCLUSIONS:Preexisting arterial intimal hyperplasia is not associated with the 6-week AVF blood flow, diameter or stenosis, or clinical maturation when the preoperative arterial diameter is ≥2 mm.

Dataset Information

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

Publications

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

Similar Datasets

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