Uncoupling of glycolysis from glucose oxidation accompanies the development of heart failure with preserved ejection fraction.
Uncoupling of glycolysis from glucose oxidation accompanies the development of heart failure with preserved ejection fraction.
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DOI：
10.1186/s10020-018-0005-x
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发表时间：
2018-03-15
期刊：
影响因子：
--
通讯作者：
Lopaschuk GD
中科院分区：
文献类型：
--
作者：
Fillmore N;Levasseur JL;Fukushima A;Wagg CS;Wang W;Dyck JRB;Lopaschuk GD
心脏能量代谢的改变有助于心力衰竭（HF）的发展和严重程度。在重度HF中，总体线粒体氧化代谢显著降低，导致能量储备减少。然而，尽管在我们的社会中，射血分数保留的HF（HFpEF）的患病率很高，但尚不清楚HFpEF中心脏能量代谢发生了什么变化，以及能量代谢的改变是否有助于收缩功能障碍的发展。我们直接评估了高盐饮食（HSD）喂养3周、6周和9周的Dahl盐敏感大鼠在HFpEF发展过程中的总体能量代谢。在9周的过程中，HSD引起舒张功能的进行性降低（通过超声心动图评估E '/A'来评估）。这伴随着心脏糖酵解速率的进行性增加（在HSD第3、6和9周获得的离体工作心脏中进行评估）。相反，糖酵解（葡萄糖氧化）中丙酮酸的后续氧化没有改变，导致葡萄糖代谢的解偶联和质子产生的显着增加。增加葡萄糖转运蛋白（GLUT）1的表达伴随着这种糖酵解的升高。在早期HF中未观察到心脏脂肪酸氧化和总体三磷酸腺苷（ATP）产生率降低，但随着HF进展为EF降低的HF（即HSD 9周），两者均显著降低。总的来说，我们发现糖酵解增加是HFpEF发展过程中最早发生的能量代谢变化。糖酵解和葡萄糖氧化解偶联产生的质子增加可能有助于HFpEF的发展。本文的在线版本（10.1186/s10020-018-0005-x）包含补充材料，可供授权用户使用。
Alterations in cardiac energy metabolism contribute to the development and severity of heart failure (HF). In severe HF, overall mitochondrial oxidative metabolism is significantly decreased resulting in a reduced energy reserve. However, despite the high prevalence of HF with preserved ejection fraction (HFpEF) in our society, it is not clear what changes in cardiac energy metabolism occur in HFpEF, and whether alterations in energy metabolism contribute to the development of contractile dysfunction. We directly assessed overall energy metabolism during the development of HFpEF in Dahl salt-sensitive rats fed a high salt diet (HSD) for 3, 6 and 9 weeks. Over the course of 9 weeks, the HSD caused a progressive decrease in diastolic function (assessed by echocardiography assessment of E’/A’). This was accompanied by a progressive increase in cardiac glycolysis rates (assessed in isolated working hearts obtained at 3, 6, and 9 weeks of HSD). In contrast, the subsequent oxidation of pyruvate from glycolysis (glucose oxidation) was not altered, resulting in an uncoupling of glucose metabolism and a significant increase in proton production. Increased glucose transporter (GLUT)1 expression accompanied this elevation in glycolysis. Decreases in cardiac fatty acid oxidation and overall adenosine triphosphate (ATP) production rates were not observed in early HF, but both significantly decreased as HF progressed to HF with reduced EF (i.e. 9 weeks of HSD). Overall, we show that increased glycolysis is the earliest energy metabolic change that occurs during HFpEF development. The resultant increased proton production from uncoupling of glycolysis and glucose oxidation may contribute to the development of HFpEF. The online version of this article (10.1186/s10020-018-0005-x) contains supplementary material, which is available to authorized users.
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影响因子：
37.8
作者：
Dyck, Jason R. B.;Hopkins, Teresa A.;Lopaschuk, Gary D.
通讯作者：
Lopaschuk, Gary D.
影响因子：
5
作者：
CHESNAIS, JM;CORABOEUF, E;VASSAS, JM
通讯作者：
VASSAS, JM
影响因子：
8.3
作者：
Klotz, S;Hay, I;Burkhoff, D
通讯作者：
Burkhoff, D
影响因子：
--
作者：
ALLARD, MF;SCHONEKESS, BO;LOPASCHUK, GD
通讯作者：
LOPASCHUK, GD
DOI：
10.1016/s0735-1097(02)01967-8
发表时间：
2002-07-17
影响因子：
24
作者：
Dávila-Román, VG;Vedala, G;Gropler, RJ
通讯作者：
Gropler, RJ