title: Plin5 alleviates myocardial ischaemia/reperfusion injury by reducing oxidative stress through inhibiting the lipolysis of lipid droplets.
abstract: 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 in Plin5-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.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.|Department of Cardiology, The Sixteenth Hospital of PLA, Aletai 836500, Xinjiang Province, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Stomatology Center, Shenzhen Hospital of Southern Medical University, Shenzhen, 518000, Guangdong Province, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Sui
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Peizhen
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism; D008066:Lipolysis; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000070797:Perilipin-5 / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D018754:Ventricular Dysfunction / Q000235:genetics
chemical_list: D000070797:Perilipin-5; C511805:Plin5 protein, mouse; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt