Metabolic dysfunction in pulmonary hypertension: the expanding relevance of the Warburg effect.
Metabolic dysfunction in pulmonary hypertension: the expanding relevance of the Warburg effect.
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DOI：
10.1111/eci.12104
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发表时间：
2013-08
影响因子：
5.5
通讯作者：
Chan SY
中科院分区：
文献类型：
--
作者：
Cottrill KA;Chan SY
肺动脉高压（PH）是一种神秘的血管综合征，其特征是肺动脉压升高和肺动脉小动脉（通常是右心室）的不良重构。与肿瘤发生相似，最近的努力探索了代谢失调和PH发病机制之间的关系。我们将讨论细胞应激源如缺氧和炎症改变细胞代谢的一般机制。基于这些原则，我们将探索PH中相应代谢病理表型的发展，重点关注世卫组织I和III组，以及这些改变可能对该疾病未来治疗的影响。在PH发病过程中对肺血管和右心室代谢失调的研究，为不同的疾病触发因素如何协调终末期疾病表现提供了更统一的理解。也就是说，正如最初在各种癌症中定义的那样，Warburg效应描述了能量生产从线粒体氧化磷酸化到糖酵解的慢性转变。在许多情况下，这种Warburg表型可能作为PH进展的中心致病机制，主要驱动细胞过度增殖和对凋亡的抵抗。因此，新的治疗策略已经越来越多地追求目标Warburg表型。最后，越来越多的新技术可用于更全面地探索代谢细胞重编程的复杂性，并可能揭示驱动PH的Warburg效应之外的不同代谢途径。PH代谢失调的研究刚刚兴起，但可能提供强大的治疗手段，以在分子水平上预防甚至逆转疾病进展。
Pulmonary hypertension (PH) is an enigmatic vascular syndrome characterized by increased pulmonary arterial pressure and adverse remodeling of the pulmonary arterioles and often of the right ventricle. Drawing parallels with tumorigenesis, recent endeavors have explored the relationship between metabolic dysregulation and PH pathogenesis. We will discuss the general mechanisms by which cellular stressors such as hypoxia and inflammation alter cellular metabolism. Based on those principles, we will explore the development of a corresponding metabolic pathophenotype in PH, with a focus on WHO groups I and III, and the implications that these alterations may have for future treatment of this disease. Investigation of metabolic dysregulation in both the pulmonary vasculature and right ventricle during PH pathogenesis has provided a more unifying understanding of how disparate disease triggers coordinate end-stage disease manifestations. Namely, as defined originally in various cancers, the Warburg effect describes a chronic shift in energy production from mitochondrial oxidative phosphorylation to glycolysis. In many cases, this Warburg phenotype may serve as a central causative mechanism for PH progression, largely driving cellular hyperproliferation and resistance to apoptosis. Consequently, new therapeutic strategies have been increasingly pursued that target the Warburg phenotype. Finally, new technologies are increasingly becoming available to probe more completely the complexities of metabolic cellular reprogramming and may reveal distinct metabolic pathways beyond the Warburg effect that drive PH. Studies of metabolic dysregulation in PH are just emerging but may offer powerful therapeutic means to prevent or even reverse disease progression at the molecular level.
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影响因子：
20.1
作者：
Chan SY;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1111/j.1752-8062.2011.00301.x
发表时间：
2011-08
期刊：
Clinical and translational science
影响因子：
--
作者：
Decker I;Ghosh S;Comhair SA;Farha S;Tang WH;Park M;Wang S;Lichtin AE;Erzurum SC
通讯作者：
Erzurum SC
影响因子：
5.7
作者：
Fernandez-Friera, Leticia;Garcia-Alvarez, Ana;Sanz, Javier
通讯作者：
Sanz, Javier
影响因子：
4.8
作者：
Belmont, Peter J.;Tadimalla, Archana;Glembotski, Christopher C.
通讯作者：
Glembotski, Christopher C.