In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart.
In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart.
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DOI：
10.1093/cvr/cvs164
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发表时间：
2012-07-01
影响因子：
10.8
通讯作者：
Tyler DJ
中科院分区：
文献类型：
--
作者：
Dodd MS;Ball DR;Schroeder MA;Le Page LM;Atherton HJ;Heather LC;Seymour AM;Ashrafian H;Watkins H;Clarke K;Tyler DJ
目的应用超极化~（13）C磁共振（13 C）波谱和电影磁共振成像（MRI）技术研究15周龄自发性高血压大鼠（SHR）心脏的代谢和功能。在这个时间点，SHR表现出高血压和向心性肥大。肥大的细胞适应之一是减少β-氧化，它以前已被证明，在响应肥大的SHR心脏开关糖酵解/葡萄糖氧化phenotype.Methods和resultsCine-MRI（磁共振成像）被用来评估心脏功能和心脏肥大的程度。Wistar大鼠作为对照。SHR表现出每搏输出量、心率和晚期舒张期峰值充盈的功能变化，以及显著的肥大（左心室质量增加56%）。使用超极化的[1- 13 C]和[2- 13 C]丙酮酸盐，在SHR心脏中观察到通过丙酮酸脱氢酶（PDH）的13 C标记通量增加了85%，并且13 C标记掺入柠檬酸盐、乙酰肉毒碱和谷氨酸盐池的量与PDH通量的增加成比例升高。这些发现证实了使用PDH活性和蛋白质表达的PDH regulatory enzymes.ConclusionsFunctional和结构的改变在SHR心脏的生化分析是一致的肥大表型。Ourin vivowork表明SHR心脏对葡萄糖代谢的偏好，远离主要的脂肪酸氧化代谢。有趣的是，13 C标记流入乳酸是不变的，表明没有转换到厌氧糖酵解表型，而是增加了对葡萄糖氧化在SHR心脏的依赖。
AimsThe aim of this work was to use hyperpolarized carbon-13 (13C) magnetic resonance (MR) spectroscopy and cine MR imaging (MRI) to assessin vivocardiac metabolism and function in the 15-week-old spontaneously hypertensive rat (SHR) heart. At this time point, the SHR displays hypertension and concentric hypertrophy. One of the cellular adaptations to hypertrophy is a reduction in β-oxidation, and it has previously been shown that in response to hypertrophy the SHR heart switches to a glycolytic/glucose-oxidative phenotype.Methods and resultsCine-MRI (magnetic resonance imaging) was used to assess cardiac function and degree of cardiac hypertrophy. Wistar rats were used as controls. SHRs displayed functional changes in stroke volume, heart rate, and late peak-diastolic filling alongside significant hypertrophy (a 56% increase in left ventricular mass). Using hyperpolarized [1-13C] and [2-13C]pyruvate, an 85% increase in13C label flux through pyruvate dehydrogenase (PDH) was seen in the SHR heart and13C label incorporation into citrate, acetylcarnitine, and glutamate pools was elevated in proportion to the increase in PDH flux. These findings were confirmed using biochemical analysis of PDH activity and protein expression of PDH regulatory enzymes.ConclusionsFunctional and structural alterations in the SHR heart are consistent with the hypertrophied phenotype. Ourin vivowork indicates a preference for glucose metabolism in the SHR heart, a move away from predominantly fatty acid oxidative metabolism. Interestingly,13C label flux into lactate was unchanged, indicating no switch to an anaerobic glycolytic phenotype, but rather an increased reliance on glucose oxidation in the SHR heart.