Perilipin1 deficiency in whole body or bone marrow-derived cells attenuates lesions in atherosclerosis-prone mice.

Xiaojing Zhao,Jinhan He,Guoheng Xu,George Liu,Ling Zhang,Bin Geng,Ying Lyu,Mingming Gao,Liangqiang Zou,Christian Schulz

doi:10.1371/journal.pone.0123738

Abstract

AimsThe objective of this study is to determine the role of perilipin 1 (Plin1) in whole body or bone marrow-derived cells on atherogenesis.Methods and ResultsAccumulated evidence have indicated the role of Plin1 in atherosclerosis, however, these findings are controversial. In this study, we showed that Plin1 was assembled and colocalized with CD68 in macrophages in atherosclerotic plaques of ApoE-/- mice. We further found 39% reduction of plaque size in the aortic roots of Plin1 and ApoE double knockout (Plin1-/-ApoE-/-) females compared with ApoE-/- female littermates. In order to verify whether this reduction was macrophage-specific, the bone marrow cells from wild-type or Plin1 deficient mice (Plin1-/-) were transplanted into LDL receptor deficient mice (LDLR-/-). Mice receiving Plin1-/- bone marrow cells showed also 49% reduction in aortic atherosclerotic lesions compared with LDLR-/- mice received wild-type bone marrow cells. In vitro experiments showed that Plin1-/- macrophages had decreased protein expression of CD36 translocase and an enhanced cholesterol ester hydrolysis upon aggregated-LDL loading, with unaltered expression of many other regulators of cholesterol metabolism, such as cellular lipases, and Plin2 and 3. Given the fundamental role of Plin1 in protecting LD lipids from lipase hydrolysis, it is reasonably speculated that the assembly of Plin1 in microphages might function to reduce lipolysis and hence increase lipid retention in ApoE-/- plaques, but this pro-atherosclerotic property would be abrogated on inactivation of Plin1.ConclusionPlin1 deficiency in bone marrow-derived cells may be responsible for reduced atherosclerotic lesions in the mice.

Highlights

All eukaryotic cells are able to store lipids in cytosolic lipid droplets (LD) [1,2]
The full length of perilipin 1 (Plin1) protein was detected in peritoneal macrophages of mice and its expression was inducible by incubation with modified LDL (Fig 1A)
To assess the role of Plin1 in foam cell formation, the peritoneal macrophages isolated from Plin1-/- and Plin1+/+ mice were incubated with aggregated LDL (aggLDL) (50 μg/ml) for 48 h

Summary

Introduction

All eukaryotic cells are able to store lipids in cytosolic lipid droplets (LD) [1,2]. In As, macrophages take up lipids in an uncontrolled manner making them transform into foam cells, the hallmark of As[3]. Plin1(perilipin)/Plin2(adipophilin/ADRP)/Plin3(Tip47)(PAT family) were found in macrophages and foam cells [4,5,6]. In adipocytes, they were distributed in the surface of the LDs of different sizes. Plin located on the surface of LDs to protect them from lipolysis. This protective effect disappears when Plin is phosphorylated by PKA and translocated to cytoplasm [10,11]

Methods

Results

Conclusion