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Perilipin1 Deficiency in Whole Body or Bone Marrow-Derived Cells Attenuates Lesions in Atherosclerosis-Prone Mice

AIMS: The 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 RESULTS: Accumulated evidence have indicated the role of Plin1 in atherosclerosis, however, these findings are controversial. In this study, we s...

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Autores principales: Zhao, Xiaojing, Gao, Mingming, He, Jinhan, Zou, Liangqiang, Lyu, Ying, Zhang, Ling, Geng, Bin, Liu, George, Xu, Guoheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391836/
https://www.ncbi.nlm.nih.gov/pubmed/25855981
http://dx.doi.org/10.1371/journal.pone.0123738
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author Zhao, Xiaojing
Gao, Mingming
He, Jinhan
Zou, Liangqiang
Lyu, Ying
Zhang, Ling
Geng, Bin
Liu, George
Xu, Guoheng
author_facet Zhao, Xiaojing
Gao, Mingming
He, Jinhan
Zou, Liangqiang
Lyu, Ying
Zhang, Ling
Geng, Bin
Liu, George
Xu, Guoheng
author_sort Zhao, Xiaojing
collection PubMed
description AIMS: The 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 RESULTS: Accumulated 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. CONCLUSION: Plin1 deficiency in bone marrow-derived cells may be responsible for reduced atherosclerotic lesions in the mice.
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spelling pubmed-43918362015-04-21 Perilipin1 Deficiency in Whole Body or Bone Marrow-Derived Cells Attenuates Lesions in Atherosclerosis-Prone Mice Zhao, Xiaojing Gao, Mingming He, Jinhan Zou, Liangqiang Lyu, Ying Zhang, Ling Geng, Bin Liu, George Xu, Guoheng PLoS One Research Article AIMS: The 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 RESULTS: Accumulated 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. CONCLUSION: Plin1 deficiency in bone marrow-derived cells may be responsible for reduced atherosclerotic lesions in the mice. Public Library of Science 2015-04-09 /pmc/articles/PMC4391836/ /pubmed/25855981 http://dx.doi.org/10.1371/journal.pone.0123738 Text en © 2015 Zhao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhao, Xiaojing
Gao, Mingming
He, Jinhan
Zou, Liangqiang
Lyu, Ying
Zhang, Ling
Geng, Bin
Liu, George
Xu, Guoheng
Perilipin1 Deficiency in Whole Body or Bone Marrow-Derived Cells Attenuates Lesions in Atherosclerosis-Prone Mice
title Perilipin1 Deficiency in Whole Body or Bone Marrow-Derived Cells Attenuates Lesions in Atherosclerosis-Prone Mice
title_full Perilipin1 Deficiency in Whole Body or Bone Marrow-Derived Cells Attenuates Lesions in Atherosclerosis-Prone Mice
title_fullStr Perilipin1 Deficiency in Whole Body or Bone Marrow-Derived Cells Attenuates Lesions in Atherosclerosis-Prone Mice
title_full_unstemmed Perilipin1 Deficiency in Whole Body or Bone Marrow-Derived Cells Attenuates Lesions in Atherosclerosis-Prone Mice
title_short Perilipin1 Deficiency in Whole Body or Bone Marrow-Derived Cells Attenuates Lesions in Atherosclerosis-Prone Mice
title_sort perilipin1 deficiency in whole body or bone marrow-derived cells attenuates lesions in atherosclerosis-prone mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391836/
https://www.ncbi.nlm.nih.gov/pubmed/25855981
http://dx.doi.org/10.1371/journal.pone.0123738
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