Sex differences in the myocardial inflammatory response to ischemia-reperfusion injury
- 1 February 2005
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 288 (2) , E321-E326
- https://doi.org/10.1152/ajpendo.00278.2004
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/d t ) and negative (−dP/d t ) 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.Keywords
This publication has 36 references indexed in Scilit:
- Update of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesisAmerican Journal of Physiology-Renal Physiology, 2004
- P38 MAPK Mediates Myocardial Proinflammatory Cytokine Production and Endotoxin-Induced Contractile SuppressionShock, 2004
- Gender-related differences in myocardial inflammatory and contractile responses to major burn traumaAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- Liposomal Delivery of Heat Shock Protein 72 Into Renal Tubular Cells Blocks Nuclear Factor-κB Activation, Tumor Necrosis Factor-α Production, and Subsequent Ischemia-Induced ApoptosisCirculation Research, 2003
- Activation of c-Jun N-terminal kinase promotes survival of cardiac myocytes after oxidative stressBiochemical Journal, 2002
- Human Myocardial Tissue TNFαExpression Following Acute Global IschemiaIn VivoJournal of Molecular and Cellular Cardiology, 1998
- Resident Cardiac Mast Cells Degranulate and Release Preformed TNF-α, Initiating the Cytokine Cascade in Experimental Canine Myocardial Ischemia/ReperfusionCirculation, 1998
- TISSUE-SPECIFIC PROTEIN KINASE C ISOFORMS DIFFERENTIALLY MEDIATE MACROPHAGE TNFα AND IL-1β PRODUCTIONShock, 1998
- Negative Inotropic Effects of Cytokines on the Heart Mediated by Nitric OxideScience, 1992
- Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.The Journal of Experimental Medicine, 1991