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The Role of Sex Differences in Autophagy in the Heart During Coxsackievirus B3-Induced Myocarditis

Abstract

Under normal conditions, autophagy maintains cardiomyocyte health and integrity through turnover of organelles. During stress, oxygen and nutrient deprivation, or microbial infection, autophagy prolongs cardiomyocyte survival. Sex differences in induction of cell death may to some extent explain the disparity between the sexes in many human diseases. However, sex differences in gene expression, which regulate cell death and autophagy, were so far not taken in consideration to explain the sex bias of viral myocarditis. Coxsackievirus B3 (CVB3)-induced myocarditis is a sex-biased disease, with females being substantially less susceptible than males and sex hormones largely determine this bias. CVB3 was shown to induce and subvert the autophagosome for its optimal viral RNA replication. Gene expression analysis on mouse and human, healthy and CVB3-infected, cardiac samples of both sexes, suggests sex differences in autophagy-related gene expression. This review discusses the aspects of sex bias in autophagy induction in cardiomyocytes.

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Acknowledgments

We would like to thank Julie A. Dragon and Brian J. Roberts for their help with the microarray data obtained in the mouse model. This work was supported by National Institutes of Health Grants: HL108371 (SAH) and P20 GM103496-07 (RCB). The authors acknowledge the following public source for the microarray data: Genomics of Cardiovascular Development, Adaptation, and Remodeling, NHLBI Program for Genomic Applications, Harvard Medical School (url: http://www.cardiogenomics.org; accessed January 2012).

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Correspondence to Iwona A. Buskiewicz.

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Associate Editor DeLisa Fairweather oversaw the review of this article

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Koenig, A., Sateriale, A., Budd, R.C. et al. The Role of Sex Differences in Autophagy in the Heart During Coxsackievirus B3-Induced Myocarditis. J. of Cardiovasc. Trans. Res. 7, 182–191 (2014). https://doi.org/10.1007/s12265-013-9525-5

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Keywords

  • Coxsackievirus B3 (CVB3)
  • Autophagy
  • Sex bias
  • Myocarditis