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Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL\/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 \u03bcg\/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA\/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.<\/jats:p>","DOI":"10.3390\/ijms24098379","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T03:34:53Z","timestamp":1683516893000},"page":"8379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Vitamin C Regulates the Profibrotic Activity of Fibroblasts in In Vitro Replica Settings of Myocardial Infarction"],"prefix":"10.3390","volume":"24","author":[{"given":"Yichen","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine, University Hospital, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany"},{"name":"Department of Cardiology, Angiology and Intensive Care, University Hospital, RWTH Aachen, 52074 Aachen, Germany"},{"name":"Institute of Molecular Medicine, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, University Hospital, RWTH Aachen, 52074 Aachen, Germany"},{"name":"Institute of Molecular Medicine, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3232-817X","authenticated-orcid":false,"given":"Pakhwan","family":"Nilcham","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, University Hospital, RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8501-588X","authenticated-orcid":false,"given":"Octavian","family":"Bucur","sequence":"additional","affiliation":[{"name":"\u201cVictor Babes\u201d National Institute of Pathology, Splaiul Independentei nr. 99-101, Sector 5, 050096 Bucharest, Romania"},{"name":"Viron Molecular Medicine Institute, 1 Boston Place, Ste 2600, Boston, MA 02108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Vogt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, University Hospital, RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8945-4310","authenticated-orcid":false,"given":"Ioana","family":"Slabu","sequence":"additional","affiliation":[{"name":"Institute of Applied Medical Engineering, Helmholtz Institute, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa Anamaria","family":"Liehn","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, University Hospital, RWTH Aachen, 52074 Aachen, Germany"},{"name":"Institute of Molecular Medicine, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark"},{"name":"\u201cVictor Babes\u201d National Institute of Pathology, Splaiul Independentei nr. 99-101, Sector 5, 050096 Bucharest, Romania"},{"name":"National Heart Center Singapore, 5 Hospital Dr., Singapore 169609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Rusu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, University Hospital, RWTH Aachen, 52074 Aachen, Germany"},{"name":"Institute of Applied Medical Engineering, Helmholtz Institute, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16744","DOI":"10.1038\/s41598-019-53351-7","article-title":"Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction","volume":"9","author":"Rusu","year":"2019","journal-title":"Sci. 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