Molecular mechanisms of heart failure: insights from Drosophila.
Molecular mechanisms of heart failure: insights from Drosophila.
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心力衰竭的分子机制：来自果蝇的见解
DOI：
10.1007/s10741-016-9590-3
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发表时间：
2017-01
影响因子：
4.6
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Zhu S;Han Z;Luo Y;Chen Y;Zeng Q;Wu X;Yuan W
心力衰竭给全世界的卫生和经济系统带来了巨大的负担。这是一种复杂的疾病，深受遗传和环境因素的影响。无论是心衰的分子机制还是有效的预防策略都没有被完全理解。幸运的是，人类心力衰竭的相关方面可以在可控制的模型动物中进行实验研究，包括果蝇，允许在体内应用强大而复杂的分子遗传学和生理学方法。与人类一样，果蝇的心力衰竭可分为扩张型心肌病和肥厚型心肌病。重要的是，从果蝇到人类，许多指导心脏发育和功能的基因和细胞途径在进化上是保守的。衰老与心力衰竭相关的分子机制研究表明，参与衰老相关能量稳态和氧化应激抵抗的基因通过干扰IGF和TOR途径影响心功能障碍。重要的是，与哺乳动物心脏衰老有关的离子通道蛋白、细胞骨架蛋白和整合素已被证明在心力衰竭中发挥重要作用。许多先前被描述为在果蝇心脏发育中起作用的基因，如参与Wnt信号通路的基因，最近被证明在成年果蝇心脏中起重要作用。此外，由于技术限制，苍蝇模型为目前无法在哺乳动物心脏中进行的创新研究提供了机会。在这篇综述中，我们讨论了影响成年果蝇心脏和心力衰竭的基因、蛋白质和分子机制的研究进展。
Heart failure places an enormous burden on health and economic systems worldwide. It is a complex disease that is profoundly influenced by both genetic and environmental factors. Neither the molecular mechanisms underlying heart failure nor effective prevention strategies are fully understood. Fortunately, relevant aspects of human heart failure can be experimentally studied in tractable model animals, including the fruit fly, Drosophila, allowing the in vivo application of powerful and sophisticated molecular genetic and physiological approaches. Heart failure in Drosophila, as in humans, can be classified into dilated cardiomyopathies and hypertrophic cardiomyopathies. Critically, many genes and cellular pathways directing heart development and function are evolutionarily conserved from Drosophila to humans. Studies of molecular mechanisms linking aging with heart failure have revealed that genes involved in aging-associated energy homeostasis and oxidative stress resistance influence cardiac dysfunction through perturbation of IGF and TOR pathways. Importantly, ion channel proteins, cytoskeletal proteins, and integrins implicated in aging of the mammalian heart have been shown to play significant roles in heart failure. A number of genes previously described having roles in development of the Drosophila heart, such as genes involved in Wnt signaling pathways, have recently been shown to play important roles in the adult fly heart. Moreover, the fly model presents opportunities for innovative studies that cannot currently be pursued in the mammalian heart because of technical limitations. In this review, we discuss progress in our understanding of genes, proteins, and molecular mechanisms that affect the Drosophila adult heart and heart failure.