Endothelial cysteinyl leukotriene 2 receptor expression and myocardial ischemia/reperfusion injury.
Myocardial infarction with associated reperfusion injury results most commonly from complications of atherothrombosis combined with leukocyte-mediated oxidative damage and inflammatory events. The consequences can be devastating owing to the high risk for mortality or loss of quality of life from ensuing heart failure. Therefore, understanding and controlling the inflammatory response that leads to myocardial injury are of paramount importance for better therapies. Cysteinyl leukotrienes are well known lipid mediators of inflammation. They exert their cellular actions via several distinct G-protein-coupled receptors. The detection of the cysteinyl leukotriene 2 receptor (CysLT(2)R) within the heart and vasculature has led to studies to investigate its role in myocardial ischemia/reperfusion injury. Recent experiments with induced mutant mouse models have revealed that excessive CysLT(2)R activation in vascular endothelium controls vascular permeability and determines the extent of myocardial injury. Development of specific CysLT(2)R antagonists should be encouraged to study this in greater detail in preclinical animal models.
Moos
Michael P W
MP
Department of Physiology, Queen's University, Kingston, ON Canada.
Funk
Colin D
CD
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D015289:Leukotrienes / Q000096:biosynthesis*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000187:drug effects / Q000378:metabolism*
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D018077:Receptors, Leukotriene; C412375:cysteinyl leukotriene receptor 2