HIF-1, Metabolism, and Diabetes in the Embryonic and Adult Heart.
HIF-1, Metabolism, and Diabetes in the Embryonic and Adult Heart.
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DOI：
10.3389/fendo.2018.00460
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发表时间：
2018
影响因子：
5.2
通讯作者：
Pavlinkova G
中科院分区：
文献类型：
--
作者：
Cerychova R;Pavlinkova G
心脏能够代谢任何底物，这取决于其可用性，以满足其能量需求。在正常生理条件下，约95%的ATP由氧化磷酸化产生，其余由糖酵解产生。心脏代谢经历重编程以响应各种生理和病理生理条件。缺氧诱导因子1（HIF-1）介导机体对缺氧和缺血的代谢适应，包括氧化代谢向糖酵解代谢的转变。在胚胎发育过程中，HIF-1保护胚胎免受宫内缺氧，其缺失以及其强制表达具有胚胎致死性。当心脏从无氧代谢转换为有氧代谢时，HIF-1活性的降低在围产期重塑过程中至关重要。在成人心脏中，HIF-1可防止缺氧，尽管其在心肌细胞中的缺失即使在含氧量正常的条件下也会影响心脏功能。糖尿病损害HIF-1的活化，因此，在氧限制条件下损害HIF-1介导的反应。受损的HIF-1信号可能导致母体糖尿病和成人糖尿病心肌病的致畸性。在这篇综述中，我们讨论了HIF-1在整个发育到成年期的心脏中的功能，以及HIF-1信号在糖尿病中的失调及其对胚胎和成人心脏的影响。
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.
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影响因子：
8.2
作者：
Boudina, Sihem;Abel, Evan Dale
通讯作者：
Abel, Evan Dale
影响因子：
3.3
作者：
Bohuslavova, Romana;Skvorova, Lada;Pavlinkova, Gabriela
通讯作者：
Pavlinkova, Gabriela
影响因子：
3.7
作者：
Bekeredjian R;Walton CB;MacCannell KA;Ecker J;Kruse F;Outten JT;Sutcliffe D;Gerard RD;Bruick RK;Shohet RV
通讯作者：
Shohet RV
影响因子：
9.3
作者：
Cerychova R;Bohuslavova R;Papousek F;Sedmera D;Abaffy P;Benes V;Kolar F;Pavlinkova G
通讯作者：
Pavlinkova G
影响因子：
64.5
作者：
Cramer, T;Yamanishi, Y;Johnson, RS
通讯作者：
Johnson, RS