| First Author | Zhou PL | Year | 2019 |
| Journal | J Cell Biochem | Volume | 120 |
| Issue | 11 | Pages | 19107-19123 |
| PubMed ID | 31297870 | Mgi Jnum | J:294680 |
| Mgi Id | MGI:6457178 | Doi | 10.1002/jcb.29238 |
| Citation | Zhou PL, et al. (2019) Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress. J Cell Biochem 120(11):19107-19123 |
| abstractText | Excessive plasma triglyceride (TG) 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 fl 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 TG, total cholesterol, and low-density lipoprotein cholesterol levels and reduced high-density lipoprotein cholesterol contents. ApoE(-/-) Plin5(-/-) exhibited a higher number of inflammatory monocytes and neutrophils, as well as overexpression of cytokines and chemokines linked with an inflammatory response. Consistently, the IkappaBalpha/nuclear factor kappa B 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. 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 and mitogen-activated protein kinases pathways. In vitro, oxidized low-density lipoprotein (ox-LDL) 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. |
