Plin5 alleviates myocardial ischaemia/reperfusion injury by reducing oxidative stress through inhibiting the lipolysis of lipid droplets.
Plin5 alleviates myocardial ischaemia/reperfusion injury by reducing oxidative stress through inhibiting the lipolysis of lipid droplets.
复制标题
Plin5通过抑制脂滴的脂肪分解减少氧化应激减轻心肌缺血/再灌注损伤
DOI：
10.1038/srep42574
复制
发表时间：
2017-02-20
影响因子：
4.6
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Zheng P;Xie Z;Yuan Y;Sui W;Wang C;Gao X;Zhao Y;Zhang F;Gu Y;Hu P;Ye J;Feng X;Zhang L
心肌缺血再灌注（I/R）损伤是一个复杂的病理生理过程。目前的研究表明，能量代谢紊乱是心肌I/R损伤的主要病理基础，而脂肪酸的异常消耗与能量代谢紊乱密切相关。脂滴（LD）是脂质代谢相关蛋白的重要调节因子。在脂滴蛋白中，perilipin家族成员通过不同的机制调节脂肪分解和脂肪生成。Plin5是一种重要的脂外蛋白，可促进LD生成，降低脂肪酸氧化，从而保护心肌免受脂肪毒性。本研究探讨Plin5对I/R心肌的保护作用。我们的研究结果表明，Plin5缺乏增加了心肌梗死面积，加重了左心室收缩功能障碍，减少了脂质储存，增加了游离脂肪酸。plin5缺陷心肌表现为线粒体严重受损，活性氧（ROS）和丙二醛（MDA）水平升高，超氧化物歧化酶（SOD）活性降低。此外，在plin5缺失的心肌细胞中，PI3K/Akt磷酸化降低可能导致I/R损伤加重。综上所述，Plin5作为一种新的心肌脂质代谢调节剂，通过抑制细胞内脂滴的脂解来减少游离脂肪酸过氧化，从而对I/R损伤提供心脏保护，为I/R疾病的治疗方案提供新的思路。
Myocardial ischaemia-reperfusion (I/R) injury is a complex pathophysiological process. Current research has suggested that energy metabolism disorders, of which the abnormal consumption of fatty acids is closely related, compose the main pathological basis for myocardial I/R injury. Lipid droplets (LD) are critical regulators of lipid metabolism by LD-associated proteins. Among the lipid droplet proteins, the perilipin family members regulate lipolysis and lipogenesis through different mechanisms. Plin5, an important perilipin protein, promotes LD generation and lowers fatty acid oxidation, thus protecting the myocardium from lipotoxicity. This study investigated the protective effects of Plin5 in I/R myocardium. Our results indicated that Plin5 deficiency exacerbated the myocardial infarct area, aggravated left ventricular systolic dysfunction, reduced lipid storage, and elevated free fatty acids. Plin5-deficient myocardium exhibited severely damaged mitochondria, elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity. Furthermore, the decreased phosphorylation of PI3K/Akt inPlin5-null cardiomyocytes might contribute to I/R injury aggravation. In conclusion, Plin5, a new regulator of myocardial lipid metabolism, decreases free fatty acid peroxidation by inhibiting the lipolysis of intracellular lipid droplets, thus providing cardioprotection against I/R injury and shedding new light on therapeutic solutions for I/R diseases.