Redox à la carte: Novel chemogenetic models of heart failure.
Redox à la carte: Novel chemogenetic models of heart failure.
复制标题
氧化还原点菜：心力衰竭的新型化学遗传学模型。
DOI：
10.1111/bph.15093
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发表时间：
2020
影响因子：
7.3
通讯作者：
Michel,Thomas
中科院分区：
文献类型：
--
作者：
Sorrentino,Andrea;Michel,Thomas
许多目前的心力衰竭动物模型受到内在方法复杂性的阻碍，而其他模型即使经过长时间的体内治疗也只能产生微妙的心脏表型。一种新的心力衰竭“化学遗传学”动物模型再现了许多导致人类心力衰竭的疾病状态共有的一个关键特征：心脏氧化还原应激增加。这种“化学发生”方法利用了一种重组酵母酶，该酶可以在体内动态和特异性激活，在心肌细胞中产生活性氧过氧化氢（H2O2）。氧化还原应激可以通过心肌细胞中ROS的化学发生产生而被快速、选择性和可逆地操纵，从而产生一种新的扩张型心肌病模型。用血管紧张素受体拮抗剂缬沙坦治疗动物促进心室功能的恢复和不良心脏重构的解决。这篇小型综述讨论了体内化学发生方法来操纵和分析心脏中的氧化应激。
Many current animal models of heart failure are hampered by intrinsic methodological complexities, while other models yield only a subtle cardiac phenotype even after prolonged in vivo treatments. A new ‘chemogenetic’ animal model of heart failure reproduces a critical characteristic shared by many disease states that lead to heart failure in humans:an increase in redox stress in the heart.This ‘chemogenetic’ approach exploits a recombinant yeast enzyme that can be dynamically and specifically activated in vivo to generate the ROS hydrogen peroxide (H2O2) in cardiac myocytes. Redox stress can be rapidly, selectively and reversibly manipulated by chemogenetic generation of ROS in cardiac myocytes, yielding a new model of dilated cardiomyopathy. Treatment of animals with the angiotensin receptor antagonist valsartan promotes recovery of ventricular function and resolution of adverse cardiac remodelling. This mini‐review discusses in vivo chemogenetic approaches to manipulate and analyse oxidative stress in the heart.