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In this study, we sought to determine how cardiac fibroblasts were altered post-experimental myocardial infarction (MI). Female C57BL6 mice underwent experimental MI by permanent left coronary artery ligation. Cardiac fibroblasts were isolated from extracted heart tissue of experimental MI mice and subsequently treated with the pro-fibrotic cytokine, TGF-\u03b2, for 24 h and analysed using high throughput LC-MS\/MS analysis. Findings were validated using mass spectrometry data generated from human left ventricular tissue analysis, which were collected from patients with ischaemic cardiomyopathy (ISCM) and age\/sex-matched patients without clinical HF (NF). Proteomic analysis revealed significant protein expression changes in mouse cardiac fibroblasts after MI. These changes were most pronounced at 1 month post-MI, compared to earlier time points (3 days and 1 week). TGF-\u03b2 treatment profoundly affected fibroblast cells extracted from MI mice, indicating a heightened sensitivity to pro-fibrotic factors after myocardial injury. Extracellular matrix (ECM) proteins significantly altered in MI fibroblasts following TGF-\u03b2 treatment were significantly associated with cardiac remodelling. Notably, Lox was significantly changed in both isolated fibroblasts treated with TGF-\u03b2 from experiment MI mice and human ISCM. Isolated cardiac fibroblasts from MI mice are more susceptible to developing pathogenic traits following TGF-\u03b2 treatment than isolated fibroblasts from normal heart tissue. ECM proteins associated with these enhanced fibroblast activities and functions are evident. These altered proteins may play a functional role in MI-associated cardiac dysfunction.<\/jats:p>","DOI":"10.3390\/ijms26083846","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T06:23:56Z","timestamp":1744957436000},"page":"3846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteome Alterations in Cardiac Fibroblasts: Insights from Experimental Myocardial Infarction and Clinical Ischaemic Cardiomyopathy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-1976","authenticated-orcid":false,"given":"Adam","family":"Russell-Hallinan","sequence":"first","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Tonry","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9185-4666","authenticated-orcid":false,"given":"Lauren","family":"Kerrigan","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Edgar","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3941-9653","authenticated-orcid":false,"given":"Patrick","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"McDonald","sequence":"additional","affiliation":[{"name":"STOP-HF Unit, St Vincent\u2019s University Hospital Healthcare Group, D04 T6F4 Dublin, Ireland"},{"name":"UCD Conway Institute, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ledwidge","sequence":"additional","affiliation":[{"name":"STOP-HF Unit, St Vincent\u2019s University Hospital Healthcare Group, D04 T6F4 Dublin, Ireland"},{"name":"UCD Conway Institute, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Grieve","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4050-7469","authenticated-orcid":false,"given":"Narainrit","family":"Karuna","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"},{"name":"Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-0732","authenticated-orcid":false,"given":"Chris","family":"Watson","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"},{"name":"UCD Conway Institute, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Venugopal, H., Hanna, A., Humeres, C., and Frangogiannis, N.G. 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