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  • In ischemia one important signaling molecule is

    2019-07-11

    In ischemia, one important signaling molecule is hypoxia signaling factor. Maria Da Luz Sousa Fialho and coworkers [] address the signaling pathways of HIF and its effect on cardiac metabolism. As HIF is one of the drivers of metabolic changes in ischemia and myocardial infarction the authors summarize the effects of HIF signaling on uptake of fatty acids as well as glucose and analyze the effects on the metabolism of these substrates. The authors present an overview on HIF research and HIF targeting drugs and indicate why HIF may be an attractive target for therapy of cardiac disease. A different approach to target metabolism in hypoxia is presented by the group of Andrew Murray []. In their manuscript the effects of nitrate on tissue oxygenation, fatty AZD8931 metabolism and mitochondrial function in skeletal muscle are addressed. The authors present results indicating that hypoxia induces impairment in mitochondrial respiratory function in the soleus. This impairment was abolished when nitrate was supplemented in drinking water and this effect was independent of PPARĪ± signaling. Whether such effect is also present in the heart may be an interesting question with therapeutic potential. Another unconventional but nevertheless promising approach to target mitochondrial dysfunction in ischemic or hypoxic conditions may represent alternative respiratory chain enzymes. In their manuscript Howy Jacobs and his group [] present alternative respiratory enzymes as a protection against external stressors. Alternative respiratory enzymes represent enzymes which may replace one or several complexes of the respiratory chain. Thereby they may offer pathways which are not affected by inhibitors of the respiratory chain. As an example, alternative respiratory chain enzymes are upregulated by hypoxia. This may reduce oxidative stress and improve survival in this situation. Furthermore, it has been shown that these enzymes may extend lifespan. However, alternative respiratory chain enzymes are not known from vertebrates or drosophila. Thus, their effect in mammals has only partially been investigated and remains a promising field of research.
    Introduction The MR signal of various nuclei can be detected, and in metabolic research, 1H-, 13C- and 31P-MRS are most commonly used, each method unraveling different aspects of cellular metabolism.
    Dynamic measurements
    Conclusion
    Transparency document
    Acknowledgments Tineke van de Weijer was supported by a junior fellowship by the Dutch Diabetes Foundation (grant no. 2015.81.1833) and Vera Schrauwen-Hinderling was supported by a grant from the European Research Council (ERC-2017-StG - 759161).
    Introduction Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection [1]. This new definition highlights the central role of organ dysfunction in the pathogenesis of sepsis and as a determinant of poor outcome. Sepsis, however, remains a complex and incompletely understood syndrome that covers a broad and often non-specific range of clinical signs and symptoms, and variably affected organs. A hallmark of sepsis-induced multi-organ failure is the common paucity of cell death and frequent recovery of organ function in survivors. These findings, along with other evidence, imply a metabolic shutdown rather than structural damage as a key pathophysiological mechanism. Despite advances in knowledge, sepsis remains a major global health problem estimated to affect over 30 million people every year worldwide [2]. It still carries a high mortality, significant long-term physical, psychological and cognitive disability in many survivors, and has staggering economic and societal costs. The incidence of sepsis is rising, perhaps due to an ageing population with more chronic comorbidities, and increasing medical interventions [3]. Unfortunately, multiple large-scale clinical trials performed over the last three decades have failed to yield any novel, effective therapeutic intervention. Management thus remains largely supportive with avoidance of iatrogenic harm.