An association between gene expression and better survival in female mice following myocardial infarction

Quanhai Chen, Roy Williams, Chastity L. Healy, Casey D. Wright, Steven C. Wu, Timothy D. O'Connell

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Following myocardial infarction, the prognosis for females is better than males. Estrogen is thought to be protective, but clinical trials with hormone replacement failed to show protection. Here, we sought to identify novel mechanisms that might explain this sex-based difference. By diverging from the traditional focus on sex hormones, we employed a conceptually novel approach to this question by using a non-biased approach to measure global changes in gene expression following infarction. We hypothesized that specific gene programs are initiated in the heart following infarction that might account for this sex-based difference. We induced small, medium, and large infarcts in male and female mice and measured changes in gene expression by microarray following infarction. Regardless of infarct size, survival was better in females, while mortality occurred 3-10. days following infarction in males. Two days following infarction, males developed significant ventricular dilation, the best predictor of mortality in humans. Three days following infarction, we measured gene expression by microarray, comparing male versus female and sham versus surgery/infarction. In general, our results indicate a higher relative level of gene induction in females versus males and identified programs for angiogenesis, extracellular matrix remodeling, and immune response. This pattern of gene expression was linked to less pathologic remodeling in female hearts, including increased capillary density and decreased fibrosis. In summary, our results suggest an association between improved survival and less pathologic remodeling and the relative induction of gene expression in females following myocardial infarction.

Original languageEnglish (US)
Pages (from-to)801-811
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Issue number5
StatePublished - Nov 2010


  • Heart failure
  • Microarray
  • Myocardial infarction
  • Sex/gender

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