Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

半胱氨酰白三烯信号加重实验性动脉粥样硬化性心脏病的心肌缺氧

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作者:Elena Nobili, M Dolores Salvado, Lasse Folkersen, Laura Castiglioni, Jens Kastrup, Anders Wetterholm, Elena Tremoli, Göran K Hansson, Luigi Sironi, Jesper Z Haeggström, Anders Gabrielsen

Background

Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and its response to hypoxic stress. To this end, we examined Apoe(-/-) mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2) in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling to the acute myocardial response to hypoxia.

Conclusion

Our results suggest that CysLT1 antagonists may have protective effects on the hypoxic heart, and improve the oxygen supply to areas of myocardial ischemia, for instance during episodes of sleep apnea.

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