Caffeic acid ethanolamide prevents cardiac dysfunction through sirtuin dependent cardiac bioenergetics preservation.
Caffeic acid ethanolamide prevents cardiac dysfunction through sirtuin dependent cardiac bioenergetics preservation.
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DOI：
10.1186/s12929-015-0188-1
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发表时间：
2015-09-22
影响因子：
11
通讯作者：
Su MJ
中科院分区：
文献类型：
--
作者：
Lee SY;Ku HC;Kuo YH;Yang KC;Tu PC;Chiu HL;Su MJ
心脏氧化应激、生物能量学和儿茶酚胺在心力衰竭进展中起主要作用。然而，这三个主要心力衰竭因素之间的关系还没有完全阐明。咖啡酸乙醇胺(CAEA)是一种由咖啡酸合成的具有抗氧化作用的衍生物，本研究旨在探讨其在心力衰竭发病机制中的作用。异丙肾上腺素对HL-1细胞的体外研究表明，细胞和线粒体的氧化应激增加。小鼠注射异丙肾上腺素2周后，心肌肥厚、心肌纤维化、脂质过氧化、心脏三磷酸腺苷和左心室射血分数下降，提示儿茶酚胺所致心力衰竭的氧化应激和生物能量学改变。CAEA可恢复耗氧率和三磷酸腺苷含量。此外，CAEA还可减轻异丙肾上腺素诱导的小鼠心脏重构、心脏氧化应激、心脏生物能量学和功能不全。CAEA可恢复Sirtuin1和Sirtuin3的活性，减轻包括锰超氧化物歧化酶和低氧诱导因子1-α在内的蛋白质的变化，这可能是CAEA减轻异丙肾上腺素所致心脏损伤的机制之一，因此CAEA可以预防儿茶酚胺所致的心脏损伤，因此可能是预防心力衰竭进展的一种新的治疗途径。
Cardiac oxidative stress, bioenergetics and catecholamine play major roles in heart failure progression. However, the relationships between these three dominant heart failure factors are not fully elucidated. Caffeic acid ethanolamide (CAEA), a synthesized derivative from caffeic acid that exerted antioxidative properties, was thus applied in this study to explore its effects on the pathogenesis of heart failure. In vitro studies in HL-1 cells exposed to isoproterenol showed an increase in cellular and mitochondria oxidative stress. Two-week isoproterenol injections into mice resulted in ventricular hypertrophy, myocardial fibrosis, elevated lipid peroxidation, cardiac adenosine triphosphate and left ventricular ejection fraction decline, suggesting oxidative stress and bioenergetics changes in catecholamine-induced heart failure. CAEA restored oxygen consumption rates and adenosine triphosphate contents. In addition, CAEA alleviated isoproterenol-induced cardiac remodeling, cardiac oxidative stress, cardiac bioenergetics and function insufficiency in mice. CAEA treatment recovered sirtuin 1 and sirtuin 3 activity, and attenuated the changes of proteins, including manganese superoxide dismutase and hypoxia-inducible factor 1-α, which are the most likely mechanisms responsible for the alleviation of isoproterenol-caused cardiac injury CAEA prevents catecholamine-induced cardiac damage and is therefore a possible new therapeutic approach for preventing heart failure progression.