دورية أكاديمية
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Ccn2 Deletion Reduces Cardiac Dysfunction, Oxidative Markers, and Fibrosis Induced by Doxorubicin Administration in Mice.

التفاصيل البيبلوغرافية
العنوان: Ccn2 Deletion Reduces Cardiac Dysfunction, Oxidative Markers, and Fibrosis Induced by Doxorubicin Administration in Mice.
المؤلفون: Tejera-Muñoz A; Research Unit, Complejo Hospitalario La Mancha Centro, 13600 Alcázar de San Juan, Spain.; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45004 Toledo, Spain., Cortés M; Cardiology Department, Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain., Rodriguez-Rodriguez A; Departamento de Biología de Sistemas, Universidad de Alcalá, 28871 Alcalá de Henares, Spain., Tejedor-Santamaria L; Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, 28040 Madrid, Spain.; RICORS2040, Instituto de Salud Carlos III, 28040 Madrid, Spain., Marchant V; Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, 28040 Madrid, Spain.; RICORS2040, Instituto de Salud Carlos III, 28040 Madrid, Spain., Rayego-Mateos S; Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, 28040 Madrid, Spain.; RICORS2040, Instituto de Salud Carlos III, 28040 Madrid, Spain., Gimeno-Longas MJ; Department of Cell Biology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain., Leask A; College of Dentistry, University of Saskatchewan, 105 Wiggins Road, Saskatoon, SK S7N 5E4, Canada., Nguyen TQ; Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands., Martín M; Cardiology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Cardiac Pathology Research Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Tuñón J; Cardiology Department, Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain., Rodríguez I; Cardiac Pathology Research Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Ruiz-Ortega M; Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, 28040 Madrid, Spain.; RICORS2040, Instituto de Salud Carlos III, 28040 Madrid, Spain., Rodrigues-Díez RR; RICORS2040, Instituto de Salud Carlos III, 28040 Madrid, Spain.; Department of Cell Biology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Sep 05; Vol. 25 (17). Date of Electronic Publication: 2024 Sep 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Doxorubicin*/adverse effects , Connective Tissue Growth Factor*/metabolism , Connective Tissue Growth Factor*/genetics , Fibrosis* , Mice, Knockout* , Oxidative Stress*/drug effects, Animals ; Mice ; Gene Deletion ; Male ; Myocardium/metabolism ; Myocardium/pathology ; Mice, Inbred C57BL ; Cardiotoxicity/genetics ; Cardiotoxicity/metabolism
مستخلص: Cellular Communication Network Factor 2 (CCN2) is a matricellular protein implicated in cell communication and microenvironmental signaling. Overexpression of CCN2 has been documented in various cardiovascular pathologies, wherein it may exert either deleterious or protective effects depending on the pathological context, thereby suggesting that its role in the cardiovascular system is not yet fully elucidated. In this study, we aimed to investigate the effects of Ccn2 gene deletion on the progression of acute cardiac injury induced by doxorubicin (DOX), a widely utilized chemotherapeutic agent. To this end, we employed conditional knockout (KO) mice for the Ccn2 gene (CCN2-KO), which were administered DOX and compared to DOX-treated wild-type (WT) control mice. Our findings demonstrated that the ablation of CCN2 ameliorated DOX-induced cardiac dysfunction, as evidenced by improvements in ejection fraction (EF) and fractional shortening (FS) of the left ventricle. Furthermore, DOX-treated CCN2-KO mice exhibited a significant reduction in the gene expression and activation of oxidative stress markers (Hmox1 and Nfe2l2/NRF2) relative to DOX-treated WT controls. Additionally, the deletion of Ccn2 markedly attenuated DOX-induced cardiac fibrosis. Collectively, these results suggest that CCN2 plays a pivotal role in the pathogenesis of DOX-mediated cardiotoxicity by modulating oxidative stress and fibrotic pathways. These findings provide a novel avenue for future investigations to explore the therapeutic potential of targeting CCN2 in the prevention of DOX-induced cardiac dysfunction.
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معلومات مُعتمدة: to Marta Ruiz-Ortega Sociedad Española de Cardiología; to Raul Rodrigues-Diez Sociedad Española de Arteriosclerosis; PI20/00140 and PI23/00394 Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union; RICORS2040; RD21/0005/0002 Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union; INNOREN P2022/BMD-7221 Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union; CP23/00025 Miguel Servet ISCIII program
فهرسة مساهمة: Keywords: CCN2; cardiac dysfunction; doxorubicin; fibrosis; oxidative stress
المشرفين على المادة: 80168379AG (Doxorubicin)
139568-91-5 (Connective Tissue Growth Factor)
0 (CCN2 protein, mouse)
تواريخ الأحداث: Date Created: 20240914 Date Completed: 20240914 Latest Revision: 20240917
رمز التحديث: 20240918
مُعرف محوري في PubMed: PMC11394698
DOI: 10.3390/ijms25179617
PMID: 39273564
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25179617