Testosterone and interleukin-1β increase cardiac remodeling during coxsackievirus B3 myocarditis via serpin A 3n.

American Journal of Physiology. Heart and Circulatory Physiology
Michael J CoronadoDeLisa Fairweather

Abstract

Myocarditis and dilated cardiomyopathy (DCM) are often caused by viral infections and occur more frequently in men than in women, but the reasons for the sex difference remain unclear. The aim of this study was to assess whether gene changes in the heart during coxsackievirus B3 (CVB3) myocarditis in male and female BALB/c mice predicted worse DCM in males. Although myocarditis (P = 4.2 × 10(-5)) and cardiac dilation (P = 0.008) were worse in males, there was no difference in viral replication in the heart. Fibrotic remodeling genes, such as tissue inhibitor of metalloproteinase (TIMP)-1 and serpin A 3n, were upregulated in males during myocarditis rather than during DCM. Using gonadectomy and testosterone replacement, we showed that testosterone increased cardiac TIMP-1 (P = 0.04), serpin A 3n (P = 0.007), and matrix metalloproteinase (MMP)-8 (P = 0.04) during myocarditis. Testosterone increased IL-1β levels in the heart (P = 0.02), a cytokine known to regulate cardiovascular remodeling, and IL-1β in turn increased cardiac serpin A 3n mRNA (P = 0.005). We found that 39 of 118 (33%) genes identified in acute DCM patients were significantly altered in the heart during CVB3 myocarditis in mice, including serpin A 3n (3.3-fold cha...Continue Reading

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Citations

Dec 21, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Eric D AbstonDeLisa Fairweather
Jan 10, 2014·Journal of Cardiovascular Translational Research·DeLisa FairweatherTomás R Guilarte
Jan 2, 2014·Journal of Cardiovascular Translational Research·Reid G HendryDavid J Marchant
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Jan 1, 2014·Clinical Medicine Insights. Cardiology·DeLisa Fairweather
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Mar 21, 2013·Circulation. Cardiovascular Imaging·Leslie T Cooper, DeLisa Fairweather
Oct 17, 2017·Circulation. Cardiovascular Genetics·Michael J CoronadoKatelyn A Bruno
Jul 20, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Hai-Yan PanJian-Hua Zhu
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Aug 10, 2020·Current Cardiology Reports·Domenico D'AmarioGianluigi Savarese
Jan 15, 2019·Journal of the American Heart Association·Michael J CoronadoDeLisa Fairweather
Mar 22, 2020·Redox Biology·Damian N Di FlorioDeLisa Fairweather
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Jun 3, 2021·Journal of Clinical Medicine·Angita JainDeLisa Fairweather
Jun 15, 2021·Frontiers in Immunology·Maria Luisa BarcenaVera Regitz-Zagrosek
Aug 28, 2021·International Journal of Molecular Sciences·Katelyn A BrunoDeLisa Fairweather

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