Peroxisome proliferator-activated receptor alpha is downregulated in the failing human heart.
Peroxisome proliferator-activated receptor alpha is downregulated in the failing human heart.
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过氧化物酶体增殖物激活受体α在衰竭的人类心脏中下调。
DOI：
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发表时间：
2003
影响因子：
8.3
通讯作者：
R. Smolenski
中科院分区：
文献类型：
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作者：
J. Karbowska;Z. Kochan;R. Smolenski
人类心脏肥大与心肌脂肪酸β-氧化（FAO）减少和代谢基因表达的伴随改变有关。通过心脏FAO途径的通量是成年哺乳动物心脏中能量产生的主要来源，根据能量需求严格控制。在啮齿类动物中，FAO途径受核过氧化物酶体增殖物激活受体α（PPARalpha？）控制。我们试图描述在人类心脏肥大生长过程中能量底物偏好从脂肪酸转换为葡萄糖的分子调控事件。我们分析了人心脏组织中PPARalpha蛋白的量。在取自五个对照供体心脏的左心室活检组织制备的匀浆中测量PPARalpha蛋白水平，并与移植时来自五个患有代偿性终末期心力衰竭（HF）的患者的活检组织中该转录因子的量进行比较。使用针对人PPARalpha的单克隆抗体的蛋白质印迹分析，我们观察到HF患者组中PPARalpha的平均量与供体组织中相比显著降低（54%）。这项研究表明，在衰竭的人类心脏中观察到的心脏PPARalpha转录因子基因表达的减少可能在成人心脏肥大期间脂肪酸利用的减少中发挥重要作用。
Cardiac hypertrophy in humans is associated with a decrease in myocardial fatty acid beta-oxidation (FAO) and accompanying alterations in metabolic gene expression. Flux through the cardiac FAO pathway, which is the principal source of energy production in the adult mammalian heart, is tightly controlled in accordance with energy demands. In rodents, the FAO pathway is under control of a nuclear peroxisome proliferator-activated receptor alpha (PPARalpha?. We sought to delineate the molecular regulatory events involved in the energy substrate preference switch from fatty acids to glucose during cardiac hypertrophic growth in humans. We analysed the amount of PPARalpha protein in human cardiac tissue. PPARalpha protein level was measured in homogenates prepared from left ventricular biopsies taken from five control donor hearts and compared to the amount of this transcription factor in biopsies from five patients with compensated end-stage heart failure (HF) at the time of transplantation. Using Western blot analysis with a monoclonal antibody against human PPARalpha, we observed a significant decrease (54%) in the mean amount of PPARalpha in the group of HF patients compared to that in the donor tissue. This study indicates that the decrease in cardiac PPARalpha transcription factor gene expression observed in the failing human heart could play an important role in a reduction in fatty acid utilisation by the adult heart during cardiac hypertrophy.
影响因子：
15.9
作者：
Barger, PM;Brandt, JM;Kelly, DP
通讯作者：
Kelly, DP
影响因子：
37.8
作者：
Sack, MN;Rader, TA;Kelly, DP
通讯作者：
Kelly, DP