项目来源

德国科学基金(DFG)

项目主持人

Professorin Ulrike Hendgen-Cotta

项目受资助机构

Universitätsklinikum Essen,Westdeutsches Herz-und Gefäßzentrum,Klinik für Kardiologie und Angiologie

项目编号

435304651

立项年度

2020

立项时间

未公开

项目级别

国家级

研究期限

未知 / 未知

受资助金额

未知

学科

Cardiology,Angiology

学科代码

未公开

基金类别

Research Grants

关键词

未公开

参与者

Tienush Rassaf

参与机构

未公开

项目标书摘要：The nitrite anion exerts cytoprotective effects in the hypoxic heart and in myocardial ischemia/reperfusion(I/R)injury.Experimental and first human studies revealed that the cardioprotective effects are at least in part mediated by modulation of mitochondrial function and inhibition of formation of reactive oxygen species.Mitochondria are essential end effectors of cardiomyocyte death and represent targets of death signaling pathways.Clinical trials translating basic science discoveries to reduce I/R injury into clinical practise by targeting mitochondria failed.In order to understand and to take advantage of the cardiovascular protective effects of nitrite,it is crucial to unravel the exact mechanisms of myocardial injury in the early phase of reperfusion and to identify and define respective targets.Whether and how nitrite is of significance in the protection of mitochondrial integrity and function leading to a prevention of mitochondrial-driven cardiomyocyte death in I/R injury is unclear.The following objectives will be persued:1.Determination of the effects of nitrite on structure,distribution and function of mitochondria following myocardial I/R;2.Characterization of critical molecular mechanisms in cardiomyocytes by which nitrite prevents apoptotic and necrotic pathways following hypoxia/reoxygenation;3.Investigation of the impact of nitrite on mitochondrial-driven myocardial I/R injury.

Application Abstract: The nitrite anion exerts cytoprotective effects in the hypoxic heart and in myocardial ischemia/reperfusion(I/R)injury.Experimental and first human studies revealed that the cardioprotective effects are at least in part mediated by modulation of mitochondrial function and inhibition of formation of reactive oxygen species.Mitochondria are essential end effectors of cardiomyocyte death and represent targets of death signaling pathways.Clinical trials translating basic science discoveries to reduce I/R injury into clinical practise by targeting mitochondria failed.In order to understand and to take advantage of the cardiovascular protective effects of nitrite,it is crucial to unravel the exact mechanisms of myocardial injury in the early phase of reperfusion and to identify and define respective targets.Whether and how nitrite is of significance in the protection of mitochondrial integrity and function leading to a prevention of mitochondrial-driven cardiomyocyte death in I/R injury is unclear.The following objectives will be persued:1.Determination of the effects of nitrite on structure,distribution and function of mitochondria following myocardial I/R;2.Characterization of critical molecular mechanisms in cardiomyocytes by which nitrite prevents apoptotic and necrotic pathways following hypoxia/reoxygenation;3.Investigation of the impact of nitrite on mitochondrial-driven myocardial I/R injury.