New Member of Endothelial Arsenal Against Inflammation

Durán, Walter N.; Sánchez, Fabiola A.

doi:10.1161/circresaha.116.309122

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…It was subsequently reported that vascular cells are the major source of 5-MTP [ 3 ]. 5-MTP has been regarded as a "new member of endothelial arsenal against inflammation [ 6 ]. This review will focus on endothelial 5-MTP biosynthesis, its vasoprotective functions and mechanisms of actions.…”

Section: Introductionmentioning

confidence: 99%

5-methoxytryptophan: an arsenal against vascular injury and inflammation

Kuo

Yet

et al. 2020

J Biomed Sci

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5-methoxytryptophan (5-MTP) is an endothelial factor with anti-inflammatory properties. It is synthesized from L-tryptophan via two enzymatic steps: tryptophan hydroxylase-1 (TPH-1) and hydroxyindole O-methyltransferase. Lipopolysaccharide (LPS) and pro-inflammatory cytokines suppress endothelial 5-MTP production by inhibiting TPH-1 expression. 5-MTP protects endothelial barrier function and promotes endothelial repair, while it blocks vascular smooth muscle cell migration and proliferation by inhibiting p38 MAPK activation. 5-MTP controls macrophage transmigration and activation by inhibiting p38 MAPK and NF-κB activation. 5-MTP administration attenuates arterial intimal hyperplasia, defends against systemic inflammation and prevents renal fibrosis in relevant murine models. Serum 5-MTP level is depressed in human sepsis as well as in mice with sepsis-like disorder. It is reduced in chronic kidney disease and acute myocardial infarction in humans. The reported data suggest that serum 5-MTP may be a theranostic biomarker. In summary, 5-MTP represents a new class of tryptophan metabolite which defends against inflammation and inflammation-mediated tissue damage and fibrosis. It may be a valuable lead compound for developing new drugs to treat complex human inflammatory disorders.

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Section: Introductionmentioning

confidence: 99%

5-methoxytryptophan: an arsenal against vascular injury and inflammation

Kuo

Yet

et al. 2020

J Biomed Sci

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“…In vivo and in vitro studies have shown that 5-MTP inhibits macrophage activation by hampering the activation of NF-KB mediated by p38-MAPK and blocking the release of pro-inflammatory cytokines, chemokines, and COX-2 expressions by macrophages [24,25]. Therefore, 5-MTP is considered a novel weapon against inflammation [26] as it helps in controlling fibroblast differentiation and pathological fibrosis in important organs and might prove very useful in this line of treatment.…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study

Huang,

Wen,

Zhang

et al. 2024

J. of Cardiovasc. Trans. Res.

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Background In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. Methods In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan–Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. Results Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17–0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13–0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65 years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. Conclusions Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics. Graphical Abstract

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“…These findings indicate that 5-MTP is an innate anti-inflammatory molecule ( Wu et al, 2020 ). As vascular EC is a major cellular source of circulating 5-MTP, 5-MTP is considered to be a new endothelial arsenal against inflammation ( Durán and Sánchez, 2016 ). In view of its efficacy in controlling myofibroblast differentiation and pathological fibrosis in vital organs, 5-MTP has the potential to fulfill the therapeutic gap.…”

Section: Introductionmentioning

confidence: 99%

Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite

2021

Front. Pharmacol.

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Tissue fibrosis causes debilitating human diseases such as liver cirrhosis, heart failure, chronic kidney disease and pulmonary insufficiency. It is a dynamic process orchestrated by specific subsets of monocyte-macrophages, fibroblasts, pericytes and hepatic stellate cells. Fibrosis is linked to tissue inflammation. Pro-inflammatory macrophages promote fibrosis by driving myofibroblast differentiation and macrophage myofibroblast transition. Myofibroblasts express α-smooth muscle cell actin (α-SMA) and secrete extracellular matrix (ECM) proteins notably collagen I and III. Deposition of ECM proteins at injury sites and interstitial tissues distorts normal structure and impairs vital functions. Despite advances in the mechanisms of fibrosis at cellular, molecular and genetic levels, prevention and treatment of fibrotic diseases remain poorly developed. Recent reports suggest that 5-methoxytryptophan (5-MTP) is effective in attenuating injury-induced liver, kidney, cardiac and pulmonary fibrosis. It inhibits macrophage activation and blocks fibroblast differentiation to myofibroblasts. Furthermore, it inhibits hepatic stellate cell differentiation into myofibroblasts. As 5-MTP is an endogenous molecule derived from tryptophan catabolism via tryptophan hydroxylase pathway, it is well-suited as a lead compound for developing new anti-fibrotic drugs. This article provides an overview of 5-MTP synthesis, and a critical review of its anti-fibrotic activities. Its mechanisms of actions and potential therapeutic value will be discussed.

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New Member of Endothelial Arsenal Against Inflammation

Cited by 4 publications

References 26 publications

5-methoxytryptophan: an arsenal against vascular injury and inflammation

5-methoxytryptophan: an arsenal against vascular injury and inflammation

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study

Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite

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