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March 14, 2026SHILAP Revista de lepidopterología4 citationsOpen Access

The tryptophan-kynurenine pathway in cardiovascular diseases: mechanistic insights and therapeutic opportunities

WCWei ChenMSMin ShuiZWZhen Wei

Key Result

Elevated Kynurenine levels were identified as a causal risk factor for myocarditis, with an odds ratio of 1.383 indicating increased risk of cardiovascular events.

Key Points

  • The aim is to explore the role of the kynurenine pathway and its metabolites in cardiovascular diseases and their potential as therapeutic targets.
  • Systematic review of tryptophan metabolism and the kynurenine pathway.
  • Analysis of key enzymes and metabolites involved in cardiovascular diseases.
  • Discussion of metabolomics and artificial intelligence for diagnosis and treatment.
  • Key metabolites in the kynurenine pathway are dysregulated in cardiovascular disease patients.
  • Enzymes such as indoleamine 2,3-dioxygenase are critical in metabolic changes related to CVDs.
  • Potential for using kynurenine pathway markers as novel biomarkers for early diagnosis and prognosis.

PICO

P
Population
Cardiovascular diseases
I
Intervention / Comparator
Kynurenine pathway modulation
O
Primary Outcome
Risk of cardiovascular events associated with tryptophan metabolism — OR 1.383 (1.102-1.738), p=0.005

Main Result

Effect estimate: OR 1.383 (95% CI 1.102-1.738)

p-value: p=0.005

Limitations

  • Lack of clinical trial data
  • Need for further validation in human studies
  • Safety concerns regarding off-target effects of interventions

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, making them crucial to further explore their mechanisms. Beyond traditional risk factors, disturbances in tryptophan metabolism, particularly the imbalance in the kynurenine pathway (KP) which accounts for over 95% of metabolic flux—have garnered significant attention in cardiovascular research. In the human body, tryptophan is primarily metabolized through the KP. This process is catalyzed by key enzymes, indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase, which convert tryptophan into kynurenine and further downstream metabolites such as kynurenic acid and 3-hydroxykynurenine. Studies have shown that levels of multiple key metabolites in KP are dysregulated in patients with CVDs, and by participating in processes such as immune activation, inflammatory responses, reactive oxygen species production, and endothelial dysfunction, and they play a complex role in mediating the pathophysiology of various CVDs, including heart failure, atherosclerosis, and hypertension. This review will systematically outline the physiology of tryptophan metabolism and the KP, summarize how key enzymes and metabolites regulate CVDs, and explore their potential as novel biomarkers for early diagnosis and prognosis and as therapeutic targets. Additionally, the review will discuss the future applications of metabolomics and artificial intelligence in the diagnosis of CVDs and the development of new therapeutics, aiming to provide new perspectives for the prevention and treatment of CVDs.

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Cite This Study

Chen et al. (2026) studied Cardiovascular diseases. Kynurenine pathway modulation was evaluated on Risk of cardiovascular events associated with tryptophan metabolism (OR 1.383, 95% CI 1.102-1.738, p=0.005). Elevated Kynurenine levels were identified as a causal risk factor for myocarditis, with an odds ratio of 1.383 indicating increased risk of cardiovascular events.

synapsesocial.com/papers/69b4fac6b39f7826a300b66bhttps://doi.org/10.3389/fcvm.2026.1726522
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