Acute and chronic effects of physical exercise on atherosclerosis, kynurenine pathway, endothelial function and inflammation in patients with coronary artery disease: a clinical trial protocol

Coronary artery disease (CAD) is the leading cause of death worldwide. Patients with CAD exhibit increased levels of kynurenine (KYN) pathway (KP) metabolites, which are key products of tryptophan (TRP) catabolism and have been identified as predictive markers for cardiovascular events and atherosclerosis progression. However, the effects of exercise on KP metabolites and their influence on atherosclerosis and inflammation in these patients remain poorly understood. We aim to investigate exercise's acute and chronic effects on carotid intima-media thickness, KP metabolites, inflammatory markers and plasma-soluble adhesion molecules in patients with CAD. Patients with CAD aged 40-70 will undergo exercise training (three times per week for 12 weeks). A healthy reference group will also be included. Evaluations will occur at baseline and post-intervention. On the first visit, carotid artery thickness will be assessed via ultrasound before and after cardiopulmonary exercise testing. The second visit will include an endothelial function evaluation using venous occlusion plethysmography and 30 min of moderate-intensity aerobic exercise. Blood samples will be collected pre-exercise and post-exercise. Levels of KP metabolites (TRP, KYN, kynurenic acid and quinolinic acid), inflammatory cytokines (interleukin-6, tumour necrosis factor-alpha and interferon-gamma), T-cell subpopulations and soluble adhesion molecules (soluble P-selectin, soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1) will be assessed via ELISA, flow cytometry and multiplex assays, respectively. This study was approved by the Ethics Committee of Pedro Ernesto University Hospital (CAAE 81718324.3.0000.5259) and registered on ClinicalTrials.gov (NCT06579807). Dissemination of the findings will include peer-reviewed publications, conference presentations and media releases.