衰弱的心脏依赖体作为燃料
Gregory Aubert1, Ola J Martin1, Julie L Horton1
1From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University of Illinois at Chicago, Chicago, IL (E.D.L.); and Department of Medicine, Washington University School of Medicine, St. Louis, MO (P.A.C.).
当脂肪酸利用率下降时, 衰弱的心脏会转向使用体作为能量. 鉴定心力衰竭中的这些代谢变化可能会导致新的治疗方法.
科学领域:
- 心脏病学
- 代谢研究
- 生物化学
背景情况:
- 心脏衰竭的特点是缺乏能量.
- 脂肪酸的使用, 心脏的主要燃料, 减少心脏衰竭.
- 探索心肌燃料的替代来源对于开发心力衰竭疗法至关重要.
研究的目的:
- 在心脏缩和衰竭期间调查心脏能量代谢变化.
- 发现心脏衰竭的燃料利用途径的变化.
- 发现心力衰竭的新疗法.
主要方法:
- 心脏缩和衰竭的小鼠模型中的定量线粒体蛋白质组学.
- 对隔离心脏制剂进行核磁共振 (NMR) 研究.
- 对心肌样本进行基于质谱的定量代谢分析.
主要成果:
- 在心脏衰竭中参与脂肪酸利用的蛋白质的降低.
- 增加β- 酸脱酶1的表达,这是氧化中的关键酶.
- 尽管脂肪酸氧化能力降低,但在过度缩小和衰竭的心脏中,燃料偏好转向体.
结论:
- 过度缩和衰竭的心脏使用体作为ATP生产的重要燃料来源.
- 在体内确定了心脏利用的特定代谢物"生物标志".
- 进一步研究这种燃料转换的适应性或不适应性可能会揭示心力衰竭的新疗法.
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