Sex differences in the myocardial inflammatory response to ischemia-reperfusion injury

Meijing Wang, Lauren Baker, Ben M. Tsai, Kirstan K. Meldrum, Daniel R. Meldrum

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

The myocardium generates inflammatory mediators during ischemia-reperfusion (I/R), and these mediators contribute to cardiac functional depression and apoptosis. The great majority of these data have been derived from male animals and humans. Sex has a profound effect over many inflammatory responses; however, it is unknown whether sex affects the cardiac inflammatory response to acute myocardial I/R. We hypothesized the existence of inherent sex differences in myocardial function, expression of inflammatory cytokines, and activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway after I/R. Isolated rat hearts from age-matched adult males and females were perfused (Langendorff), and myocardial contractile function was continuously recorded. After I/R, myocardium was assessed for expression of TNF-α, IL-1β, and IL-6 (RT-PCR, ELISA); IL-1α and IL-10 mRNA (RT-PCR); and activation of p38 MAPK (Western blot). All indexes of postischemic myocardial function [left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal positive (+dP/dt) and negative (-dP/dt) values of the first derivative of pressure] were significantly improved in females compared with males. Compared with males, females had decreased myocardial TNF-α, IL-1β, and IL-6 (mRNA, protein) and decreased activation of p38 MAPK pathway. These data demonstrate that hearts from age-matched adult females are relatively protected against I/R injury, possibly due to a diminished inflammatory response.

Original languageEnglish (US)
Pages (from-to)E321-E326
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume288
Issue number2 51-2
DOIs
StatePublished - Feb 1 2005

Keywords

  • Myocardial infarction
  • Signal transduction
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

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