Project Details
Projekt
Nitrite protects mitochondria in myocardial ischemia/reperfusion injury
Subject Area
Cardiology, Angiology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 435304651
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.
DFG Programme
Research Grants
