Cerychova Radka, Pavlinkova Gabriela
Laboratory of Molecular Pathogenetics, Institute of Biotechnology of the Czech Academy of Sciences, Prague, Czechia.
Faculty of Science, Charles University, Prague, Czechia.
Front Endocrinol (Lausanne). 2018 Aug 15;9:460. doi: 10.3389/fendo.2018.00460. eCollection 2018.
The heart is able to metabolize any substrate, depending on its availability, to satisfy its energy requirements. Under normal physiological conditions, about 95% of ATP is produced by oxidative phosphorylation and the rest by glycolysis. Cardiac metabolism undergoes reprograming in response to a variety of physiological and pathophysiological conditions. Hypoxia-inducible factor 1 (HIF-1) mediates the metabolic adaptation to hypoxia and ischemia, including the transition from oxidative to glycolytic metabolism. During embryonic development, HIF-1 protects the embryo from intrauterine hypoxia, its deletion as well as its forced expression are embryonically lethal. A decrease in HIF-1 activity is crucial during perinatal remodeling when the heart switches from anaerobic to aerobic metabolism. In the adult heart, HIF-1 protects against hypoxia, although its deletion in cardiomyocytes affects heart function even under normoxic conditions. Diabetes impairs HIF-1 activation and thus, compromises HIF-1 mediated responses under oxygen-limited conditions. Compromised HIF-1 signaling may contribute to the teratogenicity of maternal diabetes and diabetic cardiomyopathy in adults. In this review, we discuss the function of HIF-1 in the heart throughout development into adulthood, as well as the deregulation of HIF-1 signaling in diabetes and its effects on the embryonic and adult heart.
心脏能够根据底物的可利用性代谢任何底物，以满足其能量需求。在正常生理条件下，约95%的三磷酸腺苷（ATP）由氧化磷酸化产生，其余由糖酵解产生。心脏代谢会根据各种生理和病理生理状况进行重新编程。缺氧诱导因子1（HIF-1）介导对缺氧和缺血的代谢适应，包括从氧化代谢向糖酵解代谢的转变。在胚胎发育过程中，HIF-1保护胚胎免受子宫内缺氧的影响，其缺失以及强制表达在胚胎期都是致命的。在围产期重塑期间，当心脏从无氧代谢转变为有氧代谢时，HIF-1活性的降低至关重要。在成年心脏中，HIF-1可保护心脏免受缺氧影响，尽管在心肌细胞中删除HIF-1即使在常氧条件下也会影响心脏功能。糖尿病会损害HIF-1的激活，因此在氧限制条件下会损害HIF-1介导的反应。受损的HIF-1信号传导可能导致母体糖尿病的致畸性以及成人糖尿病性心肌病。在这篇综述中，我们讨论了HIF-1在从胚胎发育到成年期心脏中的功能，以及糖尿病中HIF-1信号传导的失调及其对胚胎和成年心脏的影响。
