Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure.
Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure.
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DOI：
10.1007/s00109-010-0679-1
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发表时间：
2010-10
影响因子：
4.7
通讯作者：
Archer, Stephen L.
中科院分区：
文献类型：
--
作者：
Piao, Lin;Marsboom, Glenn;Archer, Stephen L.
关键词：
右室衰竭(RVF)是肺动脉高压(PAH)的主要死亡原因。部分肺动脉高压患者为适应性重建者，发展为右室肥厚(RVH)，但仍保留右室功能；另一些患者为适应性不良重建者，迅速发展为RVF。RVF的原因尚不清楚且研究不足，大多数PAH治疗侧重于肺血管疾病的消退。在动物模型和人类RVH中的研究表明，适应性和非适应性RVH都存在葡萄糖氧化减少和糖酵解增加。代谢从线粒体氧化代谢向能量效率较低的糖酵解代谢转变可能反映了心肌缺血。我们假设，在适应性不良的RVH中，RV缺血和转录因子激活的恶性循环导致从氧化代谢到糖酵解代谢的转变，从而最终促进RVF。通过减少缺血或加强葡萄糖氧化来中断这一循环可能是有治疗作用的。丙酮酸脱氢酶抑制剂二氯乙酸酯对实验性RVH的RV功能和代谢有良好的作用，显著改善葡萄糖氧化，增强RV功能。这提示RVH的线粒体功能障碍可能是可以治疗的。在这篇简短的综述中，我们描述了线粒体代谢受损在RVH中的作用，使用适应性(肺动脉结扎)或适应性不良(野百合碱诱导的肺动脉高压)的大鼠作为人类疾病的模型。我们将讨论RVH和RVF的可能机制、相关转录因子以及线粒体代谢疗法的潜力。
Right ventricular failure (RVF) is the leading cause of death in pulmonary arterial hypertension (PAH). Some patients with pulmonary hypertension are adaptive remodelers and develop RV hypertrophy (RVH) but retain RV function; others are maladaptive remodelers and rapidly develop RVF. The cause of RVF is unclear and understudied and most PAH therapies focus on regressing pulmonary vascular disease. Studies in animal models and human RVH suggest that there is reduced glucose oxidation and increased glycolysis in both adaptive and maladaptive RVH. The metabolic shift from oxidative mitochondrial metabolism to the less energy efficient glycolytic metabolism may reflect myocardial ischemia. We hypothesize that in maladaptive RVH a vicious cycle of RV ischemia and transcription factor activation causes a shift from oxidative to glycolytic metabolism thereby ultimately promoting RVF. Interrupting this cycle, by reducing ischemia or enhancing glucose oxidation, might be therapeutic. Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, has beneficial effects on RV function and metabolism in experimental RVH, notably improving glucose oxidation and enhancing RV function. This suggests the mitochondrial dysfunction in RVH may be amenable to therapy. In this mini review, we describe the role of impaired mitochondrial metabolism in RVH, using rats with adaptive (pulmonary artery banding) or maladaptive (monocrotaline-induced pulmonary hypertension) RVH as models of human disease. We will discuss the possible mechanisms, relevant transcriptional factors, and the potential of mitochondrial metabolic therapeutics in RVH and RVF.
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影响因子：
3.5
作者：
Daicho, Takuya;Yagi, Tatsuya;Tanonaka, Kouichi
通讯作者：
Tanonaka, Kouichi
影响因子：
2.6
作者：
Handa, Nobuhiro;Magata, Yasuhiro;Komeda, Masashi
通讯作者：
Komeda, Masashi
影响因子：
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作者：
BISHOP, SP;ALTSCHULD, RA
通讯作者：
ALTSCHULD, RA
DOI：
10.1152/ajpheart.1997.272.6.h2833
发表时间：
1997-06-01
影响因子：
4.8
作者：
Lee, JK;Kodama, I;Toyama, J
通讯作者：
Toyama, J
影响因子：
4.6
作者：
Buermans, HPJ;Redout, EM;Simonides, WS
通讯作者：
Simonides, WS