Zhu Shasha, Han Zhe, Luo Yan, Chen Yulin, Zeng Qun, Wu Xiushan, Yuan Wuzhou
The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China.
Center for Cancer and Immunology Research, Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC, 20010, USA.
Heart Fail Rev. 2017 Jan;22(1):91-98. doi: 10.1007/s10741-016-9590-3.
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.
心力衰竭给全球的健康和经济系统带来了巨大负担。它是一种复杂的疾病，受到遗传和环境因素的深刻影响。目前，我们对心力衰竭的分子机制和有效的预防策略都还没有完全了解。幸运的是，人类心力衰竭的相关方面可以在易于处理的模式动物中进行实验研究，包括果蝇，这使得强大而精密的分子遗传学和生理学方法能够在体内应用。果蝇的心力衰竭，与人类一样，可分为扩张型心肌病和肥厚型心肌病。关键的是，许多指导心脏发育和功能的基因和细胞途径在从果蝇到人类的进化过程中是保守的。对衰老与心力衰竭之间分子机制的研究表明，参与衰老相关能量稳态和抗氧化应激的基因通过干扰IGF和TOR途径影响心脏功能障碍。重要的是，在哺乳动物心脏衰老过程中涉及的离子通道蛋白、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，最近已被证明在成年果蝇心脏中发挥重要作用。此外，由于技术限制，果蝇模型为目前在哺乳动物心脏中无法进行的创新性研究提供了机会。在这篇综述中，我们讨论了在理解影响果蝇成年心脏和心力衰竭的基因、蛋白质和分子机制方面取得的进展。
