Progressive loss of creatine maintains a near normal DeltaG approximately (ATP) in transgenic mouse hearts with cardiomyopathy caused by overexpressing Gsalpha.
Progressive loss of creatine maintains a near normal DeltaG approximately (ATP) in transgenic mouse hearts with cardiomyopathy caused by overexpressing Gsalpha.
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DOI：
10.1016/j.yjmcc.2009.10.029
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发表时间：
2010-04
影响因子：
5
通讯作者：
Ingwall JS
中科院分区：
文献类型：
--
作者：
Shen W;Vatner DE;Vatner SF;Ingwall JS
衰竭心脏中的心肌 [ATP] 下降。尽管 [ATP] 下降，但维持接近正常的 ATP 水解自由能 (ΔG∼ATP) 的一种潜在补偿机制可能是心肌肌酸 (Cr) 的减少。为了测试这一点，我们使用过度表达心脏 Gsα 的转基因小鼠进行了一项纵向研究，这些小鼠缓慢发展为心肌病。使用 31P NMR 光谱测量心肌能量，并在从 5、10、17 个月大的 Gsα 和年龄匹配的同窝野生型 (WT) 小鼠分离的灌注心脏中测定等容收缩性能。在年轻的 Gsα 心脏中，收缩性能增强，心脏能量接近正常。随着年龄的增长，Gsα 心脏的收缩性能逐渐下降，[ATP] 和 [PCr] 逐渐下降，而 [Pi] 仅略有增加； WT 心脏中未观察到任何变化。 Gsα 小鼠的心肌（但不是骨骼）[Cr] 从很小的时候（1.5 个月）就开始下降。因此，尽管 [ATP] 减少，但 Gsα 心脏中的胞质 [ADP] 和 ATP 水解产生的自由能仍保持在正常水平。在供应异丙肾上腺素导致心脏做功增加期间，Gsα小鼠心脏中的心率压力乘积（RPP）和ΔG∼ATP之间的关系表明衰竭心脏的收缩成本增加。因此，我们的结果表明，心肌[Cr]和净Pi流出量的减少通过维持功能障碍心脏中接近正常的ATP水解自由能而发挥代偿作用。然而，它也增加了收缩成本，这可能导致衰竭心脏的收缩储备较低。
Myocardial [ATP] falls in the failing heart. One potential compensatory mechanism for maintaining a near normal free energy of ATP hydrolysis (ΔG∼ATP), despite a fall in [ATP], may be the reduction of myocardial creatine (Cr). To test this, we conducted a longitudinal study using transgenic mice overexpressing cardiac Gsα, which slowly developed cardiomyopathy. Myocardial energetics measured using 31P NMR spectroscopy and isovolumic contractile performance were determined in perfused hearts isolated from 5-, 10-, 17-month-old Gsα and age-matched littermate wild type (WT) mice. In young Gsα hearts, contractile performance was enhanced with near normal cardiac energetics. With age, as contractile performance progressively decreased in Gsα hearts, [ATP] and [PCr] progressively decreased while [Pi] increased only modestly; no changes were observed in WT hearts. Myocardial (but not skeletal) [Cr] in Gsα mice decreased, beginning at an early age (1.5-months). Consequently, cytosolic [ADP] and the free energy available from ATP hydrolysis were maintained at normal levels in Gsα hearts, despite decreased [ATP]. During increased cardiac work caused by supplying isoproterenol, the relationship between the rate pressure product (RPP) and ΔG∼ATP in Gsα mouse hearts demonstrated an increased cost of contraction in failing hearts. Thus, our results suggest that the decrease of myocardial [Cr] and net Pi efflux play compensatory roles by maintaining a nearly normal free energy of ATP hydrolysis in the dysfunctional heart; however, it also increased the cost of contraction, which may contribute to the lower contractile reserve in the failing heart.
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影响因子：
4.8
作者：
HARDY, CJ;WEISS, RG;GERSTENBLITH, G
通讯作者：
GERSTENBLITH, G
影响因子：
3.4
作者：
He, Huamei;Javadpour, Maryam M.;Ingwall, Joanne S.
通讯作者：
Ingwall, Joanne S.
影响因子：
37.8
作者：
Shen, WQ;Asai, K;Ingwall, JS
通讯作者：
Ingwall, JS
影响因子：
15.9
作者：
Spindler, M;Saupe, KW;Ingwall, JS
通讯作者：
Ingwall, JS
影响因子：
4.3
作者：
Starling, RC;Hammer, DF;Altschuld, RA
通讯作者：
Altschuld, RA