Perilipin 5 is protective in the ischemic heart
Perilipin 5 is protective in the ischemic heart
复制标题
DOI：
10.1016/j.ijcard.2016.06.037
复制
发表时间：
2016-09-15
影响因子：
3.5
通讯作者：
Levin, Malin C.
中科院分区：
文献类型：
--
作者：
Drevinge, Christina;Dalen, Knut T.;Levin, Malin C.
背景：心肌缺血与心脏代谢的改变有关，导致脂肪酸氧化减少和脂质积累增加。在这里，我们研究心肌脂质含量和动态如何影响缺血心脏的功能，并重点关注脂滴蛋白perilipin 5 (Plin5)在心肌缺血病理生理学中的作用。 方法和结果：我们生成Plin5(-/-)小鼠，发现Plin5缺陷显着降低了心脏中的甘油三酯含量。正常情况下，Plin5(-/-)小鼠通过减少脂肪酸摄取和增加葡萄糖摄取来维持接近正常的心脏功能，从而保持能量平衡。然而，在应激或心肌缺血期间，Plin5 缺乏导致心肌底物可用性减少、心功能严重下降和死亡率增加。重要的是，对疑似冠状动脉疾病的人类队列的分析表明，常见的非编码多态性 rs884164 会降低 PLIN5 的心脏表达，并与心肌缺血后的心脏功能下降相关，表明 Plin5 在心功能障碍中发挥作用。结论：我们的研究结果表明，Plin5 缺陷会改变心脏脂质代谢，并与心肌缺血后的生存率降低相关，表明 Plin5 在缺血后的心脏中发挥有益作用。 (C) 2016 年作者。由爱思唯尔爱尔兰有限公司出版
Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia.Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction.Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.