Sex Differences in Expression of Pro-Inflammatory Markers and miRNAs in a Mouse Model of CVB3 Myocarditis.

Autor: Estepa M; Department of Internal Medicine and Cardiology, Deutsches Herzzentrum der Charité, 13353 Berlin, Germany., Niehues MH; Institute for Gender in Medicine, Center for Cardiovascular Research, Charité University Hospital, 10115 Berlin, Germany., Vakhrusheva O; Department of Urology, University Hospital Tübingen, 72076 Tübingen, Germany., Haritonow N; Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203 Berlin, Germany., Ladilov Y; Heart Center Brandenburg, Department of Cardiovascular Surgery, Brandenburg Medical School, 16321 Bernau bei Berlin, Germany., Barcena ML; Department of Urology, University Hospital Tübingen, 72076 Tübingen, Germany., Regitz-Zagrosek V; Institute for Gender in Medicine, Center for Cardiovascular Research, Charité University Hospital, 10115 Berlin, Germany.; Department of Cardiology, University Hospital Zürich, University of Zürich, 8091 Zürich, Switzerland.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Sep 06; Vol. 25 (17). Date of Electronic Publication: 2024 Sep 06.
DOI: 10.3390/ijms25179666
Abstrakt: Myocarditis is an inflammatory disease that may lead to dilated cardiomyopathy. Viral infection of the myocardium triggers immune responses, which involve, among others, macrophage infiltration, oxidative stress, expression of pro-inflammatory cytokines, and microRNAs (miRNAs). The cardioprotective role of estrogen in myocarditis is well documented; however, sex differences in the miRNA expression in chronic myocarditis are still poorly understood, and studying them further was the aim of the present study. Male and female ABY/SnJ mice were infected with CVB3. Twenty-eight days later, cardiac tissue from both infected and control mice was used for real-time PCR and Western blot analysis. NFκB, IL-6, iNOS, TNF-α, IL-1β, MCP-1, c-fos, and osteopontin (OPN) were used to examine the inflammatory state in the heart. Furthermore, the expression of several inflammation- and remodeling-related miRNAs was analyzed. NFκB, IL-6, TNF-α, IL-1β, iNOS, and MCP-1 were significantly upregulated in male mice with CVB3-induced chronic myocarditis, whereas OPN mRNA expression was increased only in females. Further analysis revealed downregulation of some anti-inflammatory miRNA in male hearts (let7a), with upregulation in female hearts (let7b). In addition, dysregulation of remodeling-related miRNAs (miR27b and mir199a) in a sex-dependent manner was observed. Taken together, the results of the present study suggest a sex-specific expression of pro-inflammatory markers as well as inflammation- and remodeling-related miRNAs, with a higher pro-inflammatory response in male CVB3 myocarditis mice.
Databáze: MEDLINE
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