The Footprint of Kynurenine Pathway in Cardiovascular Diseases

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Abstract

Kynurenine pathway is the main route of tryptophan metabolism and produces several metabolites with various biologic properties. It has been uncovered that several cardiovascular diseases are associated with the overactivation of kynurenine pathway and kynurenine and its metabolites have diagnostic and prognostic value in cardiovascular diseases. Furthermore, it was found that several kynurenine metabolites can differently affect cardiovascular health. For instance, preclinical studies have shown that kynurenine, xanthurenic acid and cis-WOOH decrease blood pressure; kynurenine and 3-hydroxyanthranilic acid prevent atherosclerosis; kynurenic acid supplementation and kynurenine 3-monooxygenase (KMO) inhibition improve the outcome of stroke. Indoleamine 2,3-dioxygenase (IDO) overactivity and increased kynurenine levels improve cardiac and vascular transplantation outcomes, whereas exacerbating the outcome of myocardial ischemia, post-ischemic myocardial remodeling, and abdominal aorta aneurysm. IDO inhibition and KMO inhibition are also protective against viral myocarditis. In addition, dysregulation of kynurenine pathway is observed in several conditions such as senescence, depression, diabetes, chronic kidney disease (CKD), cirrhosis, and cancer closely connected to cardiovascular dysfunction. It is worth defining the exact effect of each metabolite of kynurenine pathway on cardiovascular health. This narrative review is the first review that separately discusses the involvement of kynurenine pathway in different cardiovascular diseases and dissects the underlying molecular mechanisms.

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An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

Ralph Sacco, Scott E Kasner, Joseph P Broderick … (2013)

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term "stroke" is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

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Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms

John R Petrie, Tomasz J. Guzik, Rhian M. Touyz (2018)

Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes.

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Epidemiology of cardiovascular disease in China: current features and implications

Dong Zhao, Jing Liu, Miao Wang … (2018)

Cardiovascular disease (CVD) is the leading cause of death in China. To develop effective and timely strategies to cope with the challenges of CVD epidemics, we need to understand the current epidemiological features of the major types of CVD and the implications of these features for the prevention and treatment of CVD. In this Review, we summarize eight important features of the epidemiology of CVD in China. Some features indicate a transition in CVD epidemiology owing to interrelated changes in demography, environment, lifestyle, and health care, including the rising burden from atherosclerotic CVD (ischaemic heart disease and ischaemic stroke), declining mortality from haemorrhage stroke, varied regional epidemiological trends in the subtypes of CVD, increasing numbers of patients with moderate types of ischaemic heart disease and ischaemic stroke, and increasing ageing of patients with CVD. Other features highlight the problems that need particular attention, including the high proportion of out-of-hospital death of patients with ischaemic heart disease with insufficient prehospital care; the wide gaps between guideline-recommended goals and levels of lifestyle indicators; and the huge number of patients with undiagnosed, untreated, or uncontrolled hypertension, hypercholesterolaemia, or diabetes mellitus.

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Journal

Journal ID (nlm-ta): Int J Tryptophan Res

Journal ID (iso-abbrev): Int J Tryptophan Res

Journal ID (publisher-id): TRY

Journal ID (hwp): sptry

Title: International Journal of Tryptophan Research : IJTR

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Electronic): 1178-6469

Publication date (Electronic): 28 June 2022

Publication date Collection: 2022

Volume: 15

Electronic Location Identifier: 11786469221096643

Affiliations

[1 ]School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran

[2 ]Student Research Committee, Health Research Center, Babol University of Medical Sciences, Babol, Iran

Author notes

[*]Moein Ala, School of Medicine, Tehran University of Medical Sciences (TUMS), Poursina Street, Enqhelab Square, Tehran, Iran. Email: moinala75@ 123456yahoo.com

Author information

Moein Ala https://orcid.org/0000-0001-5951-4864

Seyed Parsa Eftekhar https://orcid.org/0000-0002-1175-4380

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Publisher ID: 10.1177_11786469221096643

DOI: 10.1177/11786469221096643

PMC ID: 9248048

PubMed ID: 35784899

SO-VID: 3930408c-7a4b-4887-8c42-f2968d20151f

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This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

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Date received : 8 December 2021

Date accepted : 28 March 2022

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cover-date January-December 2022

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ScienceOpen disciplines: Biochemistry

Keywords: kynurenine pathway,cardiovascular disease,hypertension,atherosclerosis,myocardial infraction,transplantation

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ScienceOpen disciplines: Biochemistry

Keywords: kynurenine pathway, cardiovascular disease, hypertension, atherosclerosis, myocardial infraction, transplantation

The Footprint of Kynurenine Pathway in Cardiovascular Diseases

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Cardiovascular Innovations and Applications

Most cited references 249

An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms

Epidemiology of cardiovascular disease in China: current features and implications

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