{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:51:57Z","timestamp":1773251517334,"version":"3.50.1"},"reference-count":30,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"unspecified","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","award":["404204\/2023-6"],"award-info":[{"award-number":["404204\/2023-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/200.132\/2023"],"award-info":[{"award-number":["E-26\/200.132\/2023"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Sport Exerc Med"],"accepted":{"date-parts":[[2025,1,14]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>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\u2019s acute and chronic effects on carotid intima-media thickness, KP metabolites, inflammatory markers and plasma-soluble adhesion molecules in patients with CAD. <jats:named-content content-type=\"\">Patients with CAD aged <\/jats:named-content>40\u201370<jats:named-content content-type=\"\"> will undergo exercise training (three times per week for <\/jats:named-content>12 weeks<jats:named-content content-type=\"\">). 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 <\/jats:named-content>30 min<jats:named-content content-type=\"\"> 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. <\/jats:named-content>\n                  <jats:named-content content-type=\"\">This study was approved by the Ethics Committee of Pedro Ernesto University Hospital (CAAE 81718324.3.0000.5259) and registered on ClinicalTrials.gov (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06579807\">NCT06579807<\/jats:ext-link>). Dissemination of the findings will include peer-reviewed publications, conference presentations and media releases.<\/jats:named-content>\n               <\/jats:p>","DOI":"10.1136\/bmjsem-2024-002432","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T11:55:27Z","timestamp":1739188527000},"page":"e002432","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["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"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct06579807","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06579807","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Gabriela Andrade","family":"Paz","sequence":"first","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus VDS","family":"Rangel","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caio Luan","family":"Farias","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 Luiz Conveniente","family":"Soares","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Langner","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia M L","family":"Dutra","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliete","family":"Bouskela","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo","family":"Farinatti","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria das Gra\u00e7as C","family":"Souza","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-7251","authenticated-orcid":false,"given":"Juliana P","family":"Borges","sequence":"additional","affiliation":[{"name":"Rio de Janeiro State University, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"2025083110471184000_11.1.e002432.1","unstructured":"World Heart Federation . World heart report 2023: confronting the world\u2019s number one killer. 2023. Available: https:\/\/world-heart-federation.org\/wp-content\/uploads\/World-Heart-Report-2023.pdf [Accessed 13 Sep 2023]."},{"key":"2025083110471184000_11.1.e002432.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0106-z"},{"key":"2025083110471184000_11.1.e002432.3","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature New Biol"},{"key":"2025083110471184000_11.1.e002432.4","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23063346","article-title":"Pathophysiology of Atherosclerosis","volume":"23","author":"Jebari-Benslaiman","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2025083110471184000_11.1.e002432.5","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.768560","article-title":"Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease","volume":"12","author":"G\u00e1sp\u00e1r","year":"2021","journal-title":"Front Immunol"},{"key":"2025083110471184000_11.1.e002432.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2504-2"},{"key":"2025083110471184000_11.1.e002432.7","doi-asserted-by":"crossref","DOI":"10.3390\/cells12030460","article-title":"Kynurenine Pathway in Diabetes Mellitus-Novel Pharmacological Target?","volume":"12","author":"Kozie\u0142","year":"2023","journal-title":"Cells"},{"key":"2025083110471184000_11.1.e002432.8","doi-asserted-by":"crossref","first-page":"1406856","DOI":"10.3389\/fcvm.2024.1406856","article-title":"The role of the kynurenine pathway in cardiovascular disease","volume":"11","author":"Yang","year":"2024","journal-title":"Front Cardiovasc Med"},{"key":"2025083110471184000_11.1.e002432.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.07.051"},{"key":"2025083110471184000_11.1.e002432.10","doi-asserted-by":"crossref","unstructured":"Baumgartner R , Forteza MJ , Ketelhuth DFJ . The interplay between cytokines and the Kynurenine pathway in inflammation and atherosclerosis. Cytokine 2019;122. doi:10.1016\/j.cyto.2017.09.004","DOI":"10.1016\/j.cyto.2017.09.004"},{"key":"2025083110471184000_11.1.e002432.11","doi-asserted-by":"crossref","DOI":"10.3390\/metabo11080508","article-title":"Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans","volume":"11","author":"Valente-Silva","year":"2021","journal-title":"Metabolites"},{"key":"2025083110471184000_11.1.e002432.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.01.004"},{"key":"2025083110471184000_11.1.e002432.13","unstructured":"Florindo AA , Latorre MRDO . Valida\u00e7\u00e3o e reprodutibilidade do question\u00e1rio de Baecke de avalia\u00e7\u00e3o da atividade f\u00edsica habitual em homens adultos. 2003;9:121\u201335."},{"key":"2025083110471184000_11.1.e002432.14","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.e7586","article-title":"SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials","volume":"346","author":"Chan","year":"2013","journal-title":"BMJ"},{"key":"2025083110471184000_11.1.e002432.15","unstructured":"Wenger NK , Hellerstein HK . Rehabilitation of the coronary patient. New york: John wiley & sons, 1978."},{"key":"2025083110471184000_11.1.e002432.16","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-199903000-00019"},{"key":"2025083110471184000_11.1.e002432.17","unstructured":"Pescatello LS . ACSM\u2019s guidelines for exercise testing and prescription. Lippincott Williams & Wilkins, 2013."},{"key":"2025083110471184000_11.1.e002432.18","doi-asserted-by":"publisher","DOI":"10.1249\/00005768-199509000-00009"},{"key":"2025083110471184000_11.1.e002432.19","doi-asserted-by":"publisher","DOI":"10.1159\/000343145"},{"key":"2025083110471184000_11.1.e002432.20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.14366\/usg.13018","article-title":"General principles of carotid Doppler ultrasonography","volume":"33","author":"Lee","year":"2014","journal-title":"Ultrasonography"},{"key":"2025083110471184000_11.1.e002432.21","doi-asserted-by":"crossref","DOI":"10.11606\/s1518-8787.2021055002473","article-title":"Food frequency questionnaire for adults in the Brazilian Northeast region: emphasis on the level of food processing","volume":"55","author":"Motta","year":"2021","journal-title":"Rev Saude Publica"},{"key":"2025083110471184000_11.1.e002432.22","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-120420-021719"},{"key":"2025083110471184000_11.1.e002432.23","unstructured":"Glodzik J , Rewiuk K , Adamiak J , et al . Controlled aerobic training improves endothelial function and modifies vascular remodeling in healthy adults with high normal blood pressure. J Physiol Pharmacol 2018;69. doi:10.26402\/jpp.2018.5.04"},{"key":"2025083110471184000_11.1.e002432.24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0292734","article-title":"The effects of exercise training on circulating adhesion molecules in adults: A systematic review and meta-analysis","volume":"18","author":"Khalafi","year":"2023","journal-title":"PLoS One"},{"key":"2025083110471184000_11.1.e002432.25","doi-asserted-by":"crossref","DOI":"10.1186\/s12933-016-0336-2","article-title":"Effects of exercise training on carotid intima-media thickness in patients with type 2 diabetes and coronary artery disease. Influence of carotid plaques","volume":"15","author":"Byrkjeland","year":"2016","journal-title":"Cardiovasc Diabetol"},{"key":"2025083110471184000_11.1.e002432.26","doi-asserted-by":"crossref","first-page":"C818","DOI":"10.1152\/ajpcell.00580.2019","article-title":"The kynurenine connection: how exercise shifts muscle tryptophan metabolism and affects energy homeostasis, the immune system, and the brain","volume":"318","author":"Martin","year":"2020","journal-title":"Am J Physiol Cell Physiol"},{"key":"2025083110471184000_11.1.e002432.27","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-10712-0","article-title":"Skeletal muscle PGC-1\u03b11 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance","volume":"10","author":"Agudelo","year":"2019","journal-title":"Nat Commun"},{"key":"2025083110471184000_11.1.e002432.28","doi-asserted-by":"crossref","unstructured":"Cervenka I , Agudelo LZ , Ruas JL . Kynurenines: Tryptophan\u2019s metabolites in exercise, inflammation, and mental health. Science 2017;357. doi:10.1126\/science.aaf9794","DOI":"10.1126\/science.aaf9794"},{"key":"2025083110471184000_11.1.e002432.29","first-page":"855","article-title":"Effect of Exercise on Carotid Artery Intima-Media Thickness in Adults: A Systematic Review and Meta-Analysis","volume":"19","author":"Wang","year":"2022","journal-title":"J Phys Act Health"},{"key":"2025083110471184000_11.1.e002432.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(03)00097-2"}],"container-title":["BMJ Open Sport &amp; Exercise Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjsem-2024-002432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T17:47:19Z","timestamp":1756662439000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopensem.bmj.com\/lookup\/doi\/10.1136\/bmjsem-2024-002432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,2,10]]},"published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1136\/bmjsem-2024-002432"],"URL":"https:\/\/doi.org\/10.1136\/bmjsem-2024-002432","relation":{},"ISSN":["2055-7647"],"issn-type":[{"value":"2055-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]}}}