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Vascular dysfunction, an early CVD feature, is driven by oxidative stress\u2014a shared pathogenic mechanism in COPD and CVD. Carnosine, a bioactive dipeptide with antioxidant and pH-buffering properties, may enhance muscle performance and protect against vascular injury. The present study sought to determine whether carnosine supplementation combined with exercise training could modify early CVD features in a preclinical COPD model. Male BALB\/c mice were exposed to room air or cigarette smoke (CS; 9 cigarettes\/day, 5\u00a0days\/week, 8\u00a0weeks) with or without carnosine (1\u00a0mg\/ml in drinking water) and with or without treadmill exercise training (50% maximal speed; 30\u00a0min\/day, 5\u00a0days\/week). After 8\u00a0weeks, blood pressure, exercise capacity, resting heart rate, lung inflammation, systemic oxidative stress, aortic endothelial function, and platelet activation were assessed. CS impaired weight gain, reduced exercise capacity, elevated resting heart rate, and induced airway inflammation (P\u00a0&amp;lt;0.0001). CS also caused severe endothelial dysfunction and platelet activation (P\u00a0&amp;lt;0.0001). Exercise alone did not reverse these vascular abnormalities. In contrast, carnosine plus exercise restored weight gain, exercise capacity, and heart rate; preserved endothelial function; and prevented platelet adhesion and activation, without altering airway inflammation. Exercise training alone is insufficient to counteract CS-induced vascular injury. Carnosine supplementation provides synergistic vascular protection, highlighting its potential as an adjunct to PR to mitigate oxidative stress-driven CVD risk in COPD.<\/jats:p>","DOI":"10.1042\/cs20260348","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T15:26:54Z","timestamp":1776958014000},"page":"943-960","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carnosine augments the efficacy of pulmonary rehabilitation in COPD: insights from a preclinical model"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8330-7945","authenticated-orcid":false,"given":"Suleman\u00a0Abdullah","family":"Almerdasi","sequence":"first","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-9441","authenticated-orcid":false,"given":"Stanley\u00a0M.H.","family":"Chan","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-493X","authenticated-orcid":false,"given":"Rana\u00a0Abdullah","family":"Alateeq","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0403-4219","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9001-4024","authenticated-orcid":false,"given":"Simone","family":"De Luca","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5420-5859","authenticated-orcid":false,"given":"Alina","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4107-9352","authenticated-orcid":false,"given":"Kevin","family":"Mou","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4790-4811","authenticated-orcid":false,"given":"Huei\u00a0Jiunn","family":"Seow","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6533-8641","authenticated-orcid":false,"given":"Steven","family":"Bozinovski","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-7615","authenticated-orcid":false,"given":"Stavros","family":"Selemidis","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8443-7071","authenticated-orcid":false,"given":"Ross","family":"Vlahos","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"2026051511062707500_B1","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1111\/bph.16068","article-title":"Inhibition of oxidative stress by apocynin attenuated chronic obstructive pulmonary disease progression and vascular injury by cigarette smoke exposure","volume":"180","author":"Chan","year":"2023","journal-title":"Br. 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