Plin5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis and oxidative stress

• Published in: Journal of cellular biochemistry
• Main Authors: Zhou, Peng-Li, Li, Min, Han, Xin-Wei, Bi, Yong-Hua, Zhang, Wen-Guang, Wu, Zheng-Yang, Wu, Gang
• Format: Journal Article
• Language: English
• Published: United States 07.12.2017
• Subjects: atherosclerosis; apoptosis; inflammation; Plin5; oxidative stress
• ISSN: 1097-4644
• DOI: 10.1002/jcb.26493

Excessive plasma triglyceride and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism, and is involved in the regulation of oxidative stress. Although, in?ammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE ) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE mice. ApoE/Plin5 double knockout (ApoE Plin5 ) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels and reduced high-density lipoprotein cholesterol (HDLC) contents. ApoE Plin5 exhibited higher number of inflammatory monocytes and neutrophils, as well as over-expression of cytokines and chemokines linked with inflammatory response. Consistently, IκBα/nuclear factor kappa B (NF-κB) pathway was strongly activated in ApoE Plin5 . Notably, apoptosis was dramatically induced by ApoE Plin5 , as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2 (PARP-2). In addition, ApoE Plin5 contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) pathways. In vitro, oxidized low-density lipoprotein (oxLDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions. This article is protected by copyright. All rights reserved.