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.