Fatty acid oxidation enzyme gene expression is downregulated in the failing heart
Fatty acid oxidation enzyme gene expression is downregulated in the failing heart
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DOI：
10.1161/01.cir.94.11.2837
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发表时间：
1996-12-01
期刊：
影响因子：
37.8
通讯作者：
Kelly, DP
中科院分区：
文献类型：
--
作者：
Sack, MN;Rader, TA;Kelly, DP
背景在心力衰竭（HF）的发展过程中，主要的心肌能量底物从脂肪酸转变为葡萄糖。这种代谢开关，概括了胎儿心脏能量底物的偏好，被认为是维持有氧能量平衡。参与这种代谢responsibility.Methods和结果的调控机制是unknown的特征的线粒体脂肪酸β-氧化（FAG）在衰竭的心脏中的基因的表达，水平的mRNA编码的酶，催化的第一和第三步的FAO周期描绘在人心脏移植受体的左心室（LV）。与对照组相比，失败的人LV中FAO酶和mRNA水平协同下调（>40%）。在进行性LV肥大（LVH）和HF大鼠模型[SHHF/Mcc-fa（cp）（SHHF）大鼠]中表征了FAO酶基因表达变化的时间模式。与对照组相比，在SHHF大鼠的LVH和HF阶段，FAO酶mRNA水平协调下调（>70%）。相比之下，中链酰基辅酶A脱氢酶的活性和稳态水平，它催化的FAG的限速步骤，没有显着减少，直到HF阶段，表明额外的控制在翻译或翻译后水平的肥厚，但nonfailingventricular.Conclusions这些研究结果确定了一个基因调控途径参与心脏能量生产的控制在HF的发展。
Background During the development of heart failure (HF), the chief myocardial energy substrate switches from fatty acids to glucose. This metabolic switch, which recapitulates fetal cardiac energy substrate preferences, is thought to maintain aerobic energetic balance. The regulatory mechanisms involved in this metabolic response are unknown.Methods and Results To characterize the expression of genes involved in mitochondrial fatty acid beta-oxidation (FAG) in the failing heart, levels of mRNA encoding enzymes that catalyze the first and third steps of the FAO cycle were delineated in the left ventricles (LVs) of human cardiac transplant recipients. FAO enzyme and mRNA levels were coordinately downregulated (>40%) in failing human LVs compared with controls. The temporal pattern of this alteration in FAO enzyme gene expression was characterized in a rat model of progressive LV hypertrophy (LVH) and HF [SHHF/Mcc-fa(cp) (SHHF) rat]. FAO enzyme mRNA levels were coordinately downregulated (>70%) during both the LVH and HF stages in the SHHF rats compared with controls. In contrast, the activity and steady-state levels of medium-chain acyl-CoA dehydrogenase, which catalyzes a rate-limiting step in FAG, were not significantly reduced until the HF stage, indicating additional control at the translational or posttranslational levels in the hypertrophied but nonfailing ventricle.Conclusions These findings identify a gene regulatory pathway involved in the control of cardiac energy production during the development of HF.