Sex differences in the myocardial inflammatory response to ischemia-reperfusion injury.
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-alpha, IL-1beta, and IL-6 (RT-PCR, ELISA); IL-1alpha 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-alpha, IL-1beta, 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.
Wang
Meijing
M
Department of Cellular Physiology, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 215, Indianapolis, IN 46202, USA.
Baker
Lauren
L
Tsai
Ben M
BM
Meldrum
Kirstan K
KK
Meldrum
Daniel R
DR
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D004789:Enzyme Activation; D005260:Female; D008297:Male; D009206:Myocardium / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000276:immunology*; D015427:Reperfusion Injury / Q000276:immunology*; D012737:Sex Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
D016207:Cytokines; D048051:p38 Mitogen-Activated Protein Kinases