Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans

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Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans. / Baumgartner, R.; Berg, M.; Matic, L.; Polyzos, K. P.; Forteza, M. J.; Hjorth, S. A.; Schwartz, T. W.; Paulson-Berne, G.; Hansson, G. K.; Hedin, U.; Ketelhuth, D. F. J.

In: Journal of Internal Medicine, Vol. 289, No. 1, 2021, p. 53-68.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Baumgartner, R, Berg, M, Matic, L, Polyzos, KP, Forteza, MJ, Hjorth, SA, Schwartz, TW, Paulson-Berne, G, Hansson, GK, Hedin, U & Ketelhuth, DFJ 2021, 'Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans', Journal of Internal Medicine, vol. 289, no. 1, pp. 53-68. https://doi.org/10.1111/joim.13142

APA

Baumgartner, R., Berg, M., Matic, L., Polyzos, K. P., Forteza, M. J., Hjorth, S. A., Schwartz, T. W., Paulson-Berne, G., Hansson, G. K., Hedin, U., & Ketelhuth, D. F. J. (2021). Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans. Journal of Internal Medicine, 289(1), 53-68. https://doi.org/10.1111/joim.13142

Vancouver

Baumgartner R, Berg M, Matic L, Polyzos KP, Forteza MJ, Hjorth SA et al. Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans. Journal of Internal Medicine. 2021;289(1):53-68. https://doi.org/10.1111/joim.13142

Author

Baumgartner, R. ; Berg, M. ; Matic, L. ; Polyzos, K. P. ; Forteza, M. J. ; Hjorth, S. A. ; Schwartz, T. W. ; Paulson-Berne, G. ; Hansson, G. K. ; Hedin, U. ; Ketelhuth, D. F. J. / Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans. In: Journal of Internal Medicine. 2021 ; Vol. 289, No. 1. pp. 53-68.

Bibtex

@article{c07239044f8742cc8de975bcacbfd8ed,
title = "Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans",
abstract = "Background The metabolism of tryptophan (Trp) along the kynurenine pathway has been shown to carry strong immunoregulatory properties. Several experimental studies indicate that this pathway is a major regulator of vascular inflammation and influences atherogenesis. Knowledge of the role of this pathway in human atherosclerosis remains incomplete. Objectives In this study, we performed a multiplatform analysis of tissue samples,in vitroandin vivofunctional assays to elucidate the potential role of the kynurenine pathway in human atherosclerosis. Methods and results Comparison of transcriptomic data from carotid plaques and control arteries revealed an upregulation of enzymes within the quinolinic branch of the kynurenine pathway in the disease state, whilst the branch leading to the formation of kynurenic acid (KynA) was downregulated. Further analyses indicated that local inflammatory responses are closely tied to the deviation of the kynurenine pathway in the vascular wall. Analysis of cerebrovascular symptomatic and asymptomatic carotid stenosis data showed that the downregulation of KynA branch enzymes and reduced KynA production were associated with an increased probability of patients to undergo surgery due to an unstable disease.In vitro, we showed that KynA-mediated signalling through aryl hydrocarbon receptor (AhR) is a major regulator of human macrophage activation. Using a mouse model of peritoneal inflammation, we showed that KynA inhibits leukocyte recruitment. Conclusions We have found that a deviation in the kynurenine pathway is associated with an increased probability of developing symptomatic unstable atherosclerotic disease. Our study suggests that KynA-mediated signalling through AhR is an important mechanism involved in the regulation of vascular inflammation.",
keywords = "atherosclerosis, inflammation, kynurenine pathway, IDO, kynurenic acid, aryl hydrocarbon receptor, ARYL-HYDROCARBON RECEPTOR, REGULATORY T-CELLS, INDOLEAMINE 2,3-DIOXYGENASE, CARDIOVASCULAR RISK, CORONARY EVENTS, QUINOLINIC ACID, TRYPTOPHAN, ACTIVATION, INFLAMMATION, INHIBITION",
author = "R. Baumgartner and M. Berg and L. Matic and Polyzos, {K. P.} and Forteza, {M. J.} and Hjorth, {S. A.} and Schwartz, {T. W.} and G. Paulson-Berne and Hansson, {G. K.} and U. Hedin and Ketelhuth, {D. F. J.}",
year = "2021",
doi = "10.1111/joim.13142",
language = "English",
volume = "289",
pages = "53--68",
journal = "Journal of Internal Medicine",
issn = "0955-7873",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans

AU - Baumgartner, R.

AU - Berg, M.

AU - Matic, L.

AU - Polyzos, K. P.

AU - Forteza, M. J.

AU - Hjorth, S. A.

AU - Schwartz, T. W.

AU - Paulson-Berne, G.

AU - Hansson, G. K.

AU - Hedin, U.

AU - Ketelhuth, D. F. J.

PY - 2021

Y1 - 2021

N2 - Background The metabolism of tryptophan (Trp) along the kynurenine pathway has been shown to carry strong immunoregulatory properties. Several experimental studies indicate that this pathway is a major regulator of vascular inflammation and influences atherogenesis. Knowledge of the role of this pathway in human atherosclerosis remains incomplete. Objectives In this study, we performed a multiplatform analysis of tissue samples,in vitroandin vivofunctional assays to elucidate the potential role of the kynurenine pathway in human atherosclerosis. Methods and results Comparison of transcriptomic data from carotid plaques and control arteries revealed an upregulation of enzymes within the quinolinic branch of the kynurenine pathway in the disease state, whilst the branch leading to the formation of kynurenic acid (KynA) was downregulated. Further analyses indicated that local inflammatory responses are closely tied to the deviation of the kynurenine pathway in the vascular wall. Analysis of cerebrovascular symptomatic and asymptomatic carotid stenosis data showed that the downregulation of KynA branch enzymes and reduced KynA production were associated with an increased probability of patients to undergo surgery due to an unstable disease.In vitro, we showed that KynA-mediated signalling through aryl hydrocarbon receptor (AhR) is a major regulator of human macrophage activation. Using a mouse model of peritoneal inflammation, we showed that KynA inhibits leukocyte recruitment. Conclusions We have found that a deviation in the kynurenine pathway is associated with an increased probability of developing symptomatic unstable atherosclerotic disease. Our study suggests that KynA-mediated signalling through AhR is an important mechanism involved in the regulation of vascular inflammation.

AB - Background The metabolism of tryptophan (Trp) along the kynurenine pathway has been shown to carry strong immunoregulatory properties. Several experimental studies indicate that this pathway is a major regulator of vascular inflammation and influences atherogenesis. Knowledge of the role of this pathway in human atherosclerosis remains incomplete. Objectives In this study, we performed a multiplatform analysis of tissue samples,in vitroandin vivofunctional assays to elucidate the potential role of the kynurenine pathway in human atherosclerosis. Methods and results Comparison of transcriptomic data from carotid plaques and control arteries revealed an upregulation of enzymes within the quinolinic branch of the kynurenine pathway in the disease state, whilst the branch leading to the formation of kynurenic acid (KynA) was downregulated. Further analyses indicated that local inflammatory responses are closely tied to the deviation of the kynurenine pathway in the vascular wall. Analysis of cerebrovascular symptomatic and asymptomatic carotid stenosis data showed that the downregulation of KynA branch enzymes and reduced KynA production were associated with an increased probability of patients to undergo surgery due to an unstable disease.In vitro, we showed that KynA-mediated signalling through aryl hydrocarbon receptor (AhR) is a major regulator of human macrophage activation. Using a mouse model of peritoneal inflammation, we showed that KynA inhibits leukocyte recruitment. Conclusions We have found that a deviation in the kynurenine pathway is associated with an increased probability of developing symptomatic unstable atherosclerotic disease. Our study suggests that KynA-mediated signalling through AhR is an important mechanism involved in the regulation of vascular inflammation.

KW - atherosclerosis

KW - inflammation

KW - kynurenine pathway

KW - IDO

KW - kynurenic acid

KW - aryl hydrocarbon receptor

KW - ARYL-HYDROCARBON RECEPTOR

KW - REGULATORY T-CELLS

KW - INDOLEAMINE 2,3-DIOXYGENASE

KW - CARDIOVASCULAR RISK

KW - CORONARY EVENTS

KW - QUINOLINIC ACID

KW - TRYPTOPHAN

KW - ACTIVATION

KW - INFLAMMATION

KW - INHIBITION

U2 - 10.1111/joim.13142

DO - 10.1111/joim.13142

M3 - Journal article

C2 - 32794238

VL - 289

SP - 53

EP - 68

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0955-7873

IS - 1

ER -

ID: 247544603