Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE

Aims: Macrophage apoptosis is a prominent feature of atherosclerosis, yet whether cell death-protected macrophages would favour the resolution of already established atherosclerotic lesions, and thus hold therapeutic potential, remains unknown.Methods and results: We irradiated then transplanted int...

Full description

Saved in:
Bibliographic Details
Published in:Cardiovascular research 2015-09, Vol.108 (1), p.111-123
Main Authors: Bouchareychas, Laura, Pirault, John, Saint-Charles, Flora, Deswaerte, Virginie, Le Roy, Tiphaine, Jessup, Wendy, Giral, Philippe, Le Goff, Wilfried, Huby, Thierry, Gautier, Emmanuel, Lesnik, Philippe
Format: Article
Language:English
Subjects:
Animals
Antigens, Ly
Apolipoproteins E
Apoptosis
Atherosclerosis
Cell Survival
Cholesterol
Disease Progression
Life Sciences
Macrophages
Male
Mice
Proto-Oncogene Proteins c-bcl-2
Receptors, LDL
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page 123
container_issue 1
container_start_page 111
container_title Cardiovascular research
container_volume 108
creator Bouchareychas, Laura
Pirault, John
Saint-Charles, Flora
Deswaerte, Virginie
Le Roy, Tiphaine
Jessup, Wendy
Giral, Philippe
Le Goff, Wilfried
Huby, Thierry
Gautier, Emmanuel
Lesnik, Philippe
description Aims: Macrophage apoptosis is a prominent feature of atherosclerosis, yet whether cell death-protected macrophages would favour the resolution of already established atherosclerotic lesions, and thus hold therapeutic potential, remains unknown.Methods and results: We irradiated then transplanted into Apoe(-/-) or LDLr(-/-) recipient mice harbouring established atherosclerotic lesions, bone marrow cells from mice displaying enhanced macrophage survival through overexpression of the antiapoptotic gene hBcl-2 (Mø-hBcl2 Apoe(-/-) or Mø-hBcl2 Apoe(+/+) LDLr(-/-)). Both recipient mice exhibited decreased lesional apoptotic cell content and reduced necrotic areas when repopulated with Mø-hBcl2 mouse-derived bone marrow cells. In contrast, only LDLr(-/-) recipients showed a reduction in plasma cholesterol levels and in atherosclerotic lesions. The absence of significant reduction of plasma cholesterol levels in the context of apoE deficiency highlighted macrophage-derived apoE as key in both the regulation of plasma and tissue cholesterol levels and the progression of pre-existing lesion. Accordingly, hBcl2 expression in macrophages was associated with larger pools of Kupffer cells and Ly-6C(low) monocytes, both high producers of apoE. Additionally, increased Kupffer cells population was associated with improved clearance of apoptotic cells and modified lipoproteins.Conclusion: Collectively, these data show that promoting macrophage survival provides a supplemental source of apoE, which hinders pre-existing plaque progression.
doi_str_mv 10.1093/cvr/cvv177
format article
fullrecord <record><control><sourceid>hal</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_03798228v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>oai_HAL_hal_03798228v1</sourcerecordid><originalsourceid>FETCH-hal_primary_oai_HAL_hal_03798228v13</originalsourceid><addsrcrecordid>eNqVTLtuwkAQvIIIyKPhC65N4XD2gR9lFBFRpEhBb63sxXfRmbV2zQn-PiZKkTbFzGhGM6PUKjUvqansuok8IaZFMVNLY0yZ5Da3C3Uv8jXZ7bbYzNUiy02VmapcqssnU0-jP3W6h4ZpcNChljNHHyHoFgNcRQ9MHaOIp5Om42QxwYuXnxmMDpmkCROPvtEBbzXRo2M6d-7PbdIi-4ithoF2j-ruCEHw6Vcf1PP77vC2TxyEemDfA19rAl_vXz_qW2ZsUZVZVsbU_qf7DSEgWew</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE</title><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Bouchareychas, Laura ; Pirault, John ; Saint-Charles, Flora ; Deswaerte, Virginie ; Le Roy, Tiphaine ; Jessup, Wendy ; Giral, Philippe ; Le Goff, Wilfried ; Huby, Thierry ; Gautier, Emmanuel ; Lesnik, Philippe</creator><creatorcontrib>Bouchareychas, Laura ; Pirault, John ; Saint-Charles, Flora ; Deswaerte, Virginie ; Le Roy, Tiphaine ; Jessup, Wendy ; Giral, Philippe ; Le Goff, Wilfried ; Huby, Thierry ; Gautier, Emmanuel ; Lesnik, Philippe</creatorcontrib><description>Aims: Macrophage apoptosis is a prominent feature of atherosclerosis, yet whether cell death-protected macrophages would favour the resolution of already established atherosclerotic lesions, and thus hold therapeutic potential, remains unknown.Methods and results: We irradiated then transplanted into Apoe(-/-) or LDLr(-/-) recipient mice harbouring established atherosclerotic lesions, bone marrow cells from mice displaying enhanced macrophage survival through overexpression of the antiapoptotic gene hBcl-2 (Mø-hBcl2 Apoe(-/-) or Mø-hBcl2 Apoe(+/+) LDLr(-/-)). Both recipient mice exhibited decreased lesional apoptotic cell content and reduced necrotic areas when repopulated with Mø-hBcl2 mouse-derived bone marrow cells. In contrast, only LDLr(-/-) recipients showed a reduction in plasma cholesterol levels and in atherosclerotic lesions. The absence of significant reduction of plasma cholesterol levels in the context of apoE deficiency highlighted macrophage-derived apoE as key in both the regulation of plasma and tissue cholesterol levels and the progression of pre-existing lesion. Accordingly, hBcl2 expression in macrophages was associated with larger pools of Kupffer cells and Ly-6C(low) monocytes, both high producers of apoE. Additionally, increased Kupffer cells population was associated with improved clearance of apoptotic cells and modified lipoproteins.Conclusion: Collectively, these data show that promoting macrophage survival provides a supplemental source of apoE, which hinders pre-existing plaque progression.</description><identifier>ISSN: 0008-6363</identifier><identifier>DOI: 10.1093/cvr/cvv177</identifier><identifier>PMID: 26092098</identifier><language>eng</language><publisher>Oxford University Press (OUP)</publisher><subject>Animals ; Antigens, Ly ; Apolipoproteins E ; Apoptosis ; Atherosclerosis ; Cell Survival ; Cholesterol ; Disease Progression ; Life Sciences ; Macrophages ; Male ; Mice ; Proto-Oncogene Proteins c-bcl-2 ; Receptors, LDL</subject><ispartof>Cardiovascular research, 2015-09, Vol.108 (1), p.111-123</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://hal.science/hal-03798228$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bouchareychas, Laura</creatorcontrib><creatorcontrib>Pirault, John</creatorcontrib><creatorcontrib>Saint-Charles, Flora</creatorcontrib><creatorcontrib>Deswaerte, Virginie</creatorcontrib><creatorcontrib>Le Roy, Tiphaine</creatorcontrib><creatorcontrib>Jessup, Wendy</creatorcontrib><creatorcontrib>Giral, Philippe</creatorcontrib><creatorcontrib>Le Goff, Wilfried</creatorcontrib><creatorcontrib>Huby, Thierry</creatorcontrib><creatorcontrib>Gautier, Emmanuel</creatorcontrib><creatorcontrib>Lesnik, Philippe</creatorcontrib><title>Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE</title><title>Cardiovascular research</title><description>Aims: Macrophage apoptosis is a prominent feature of atherosclerosis, yet whether cell death-protected macrophages would favour the resolution of already established atherosclerotic lesions, and thus hold therapeutic potential, remains unknown.Methods and results: We irradiated then transplanted into Apoe(-/-) or LDLr(-/-) recipient mice harbouring established atherosclerotic lesions, bone marrow cells from mice displaying enhanced macrophage survival through overexpression of the antiapoptotic gene hBcl-2 (Mø-hBcl2 Apoe(-/-) or Mø-hBcl2 Apoe(+/+) LDLr(-/-)). Both recipient mice exhibited decreased lesional apoptotic cell content and reduced necrotic areas when repopulated with Mø-hBcl2 mouse-derived bone marrow cells. In contrast, only LDLr(-/-) recipients showed a reduction in plasma cholesterol levels and in atherosclerotic lesions. The absence of significant reduction of plasma cholesterol levels in the context of apoE deficiency highlighted macrophage-derived apoE as key in both the regulation of plasma and tissue cholesterol levels and the progression of pre-existing lesion. Accordingly, hBcl2 expression in macrophages was associated with larger pools of Kupffer cells and Ly-6C(low) monocytes, both high producers of apoE. Additionally, increased Kupffer cells population was associated with improved clearance of apoptotic cells and modified lipoproteins.Conclusion: Collectively, these data show that promoting macrophage survival provides a supplemental source of apoE, which hinders pre-existing plaque progression.</description><subject>Animals</subject><subject>Antigens, Ly</subject><subject>Apolipoproteins E</subject><subject>Apoptosis</subject><subject>Atherosclerosis</subject><subject>Cell Survival</subject><subject>Cholesterol</subject><subject>Disease Progression</subject><subject>Life Sciences</subject><subject>Macrophages</subject><subject>Male</subject><subject>Mice</subject><subject>Proto-Oncogene Proteins c-bcl-2</subject><subject>Receptors, LDL</subject><issn>0008-6363</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqVTLtuwkAQvIIIyKPhC65N4XD2gR9lFBFRpEhBb63sxXfRmbV2zQn-PiZKkTbFzGhGM6PUKjUvqansuok8IaZFMVNLY0yZ5Da3C3Uv8jXZ7bbYzNUiy02VmapcqssnU0-jP3W6h4ZpcNChljNHHyHoFgNcRQ9MHaOIp5Om42QxwYuXnxmMDpmkCROPvtEBbzXRo2M6d-7PbdIi-4ithoF2j-ruCEHw6Vcf1PP77vC2TxyEemDfA19rAl_vXz_qW2ZsUZVZVsbU_qf7DSEgWew</recordid><startdate>20150916</startdate><enddate>20150916</enddate><creator>Bouchareychas, Laura</creator><creator>Pirault, John</creator><creator>Saint-Charles, Flora</creator><creator>Deswaerte, Virginie</creator><creator>Le Roy, Tiphaine</creator><creator>Jessup, Wendy</creator><creator>Giral, Philippe</creator><creator>Le Goff, Wilfried</creator><creator>Huby, Thierry</creator><creator>Gautier, Emmanuel</creator><creator>Lesnik, Philippe</creator><general>Oxford University Press (OUP)</general><scope>1XC</scope></search><sort><creationdate>20150916</creationdate><title>Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE</title><author>Bouchareychas, Laura ; Pirault, John ; Saint-Charles, Flora ; Deswaerte, Virginie ; Le Roy, Tiphaine ; Jessup, Wendy ; Giral, Philippe ; Le Goff, Wilfried ; Huby, Thierry ; Gautier, Emmanuel ; Lesnik, Philippe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-hal_primary_oai_HAL_hal_03798228v13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antigens, Ly</topic><topic>Apolipoproteins E</topic><topic>Apoptosis</topic><topic>Atherosclerosis</topic><topic>Cell Survival</topic><topic>Cholesterol</topic><topic>Disease Progression</topic><topic>Life Sciences</topic><topic>Macrophages</topic><topic>Male</topic><topic>Mice</topic><topic>Proto-Oncogene Proteins c-bcl-2</topic><topic>Receptors, LDL</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bouchareychas, Laura</creatorcontrib><creatorcontrib>Pirault, John</creatorcontrib><creatorcontrib>Saint-Charles, Flora</creatorcontrib><creatorcontrib>Deswaerte, Virginie</creatorcontrib><creatorcontrib>Le Roy, Tiphaine</creatorcontrib><creatorcontrib>Jessup, Wendy</creatorcontrib><creatorcontrib>Giral, Philippe</creatorcontrib><creatorcontrib>Le Goff, Wilfried</creatorcontrib><creatorcontrib>Huby, Thierry</creatorcontrib><creatorcontrib>Gautier, Emmanuel</creatorcontrib><creatorcontrib>Lesnik, Philippe</creatorcontrib><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bouchareychas, Laura</au><au>Pirault, John</au><au>Saint-Charles, Flora</au><au>Deswaerte, Virginie</au><au>Le Roy, Tiphaine</au><au>Jessup, Wendy</au><au>Giral, Philippe</au><au>Le Goff, Wilfried</au><au>Huby, Thierry</au><au>Gautier, Emmanuel</au><au>Lesnik, Philippe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE</atitle><jtitle>Cardiovascular research</jtitle><date>2015-09-16</date><risdate>2015</risdate><volume>108</volume><issue>1</issue><spage>111</spage><epage>123</epage><pages>111-123</pages><issn>0008-6363</issn><abstract>Aims: Macrophage apoptosis is a prominent feature of atherosclerosis, yet whether cell death-protected macrophages would favour the resolution of already established atherosclerotic lesions, and thus hold therapeutic potential, remains unknown.Methods and results: We irradiated then transplanted into Apoe(-/-) or LDLr(-/-) recipient mice harbouring established atherosclerotic lesions, bone marrow cells from mice displaying enhanced macrophage survival through overexpression of the antiapoptotic gene hBcl-2 (Mø-hBcl2 Apoe(-/-) or Mø-hBcl2 Apoe(+/+) LDLr(-/-)). Both recipient mice exhibited decreased lesional apoptotic cell content and reduced necrotic areas when repopulated with Mø-hBcl2 mouse-derived bone marrow cells. In contrast, only LDLr(-/-) recipients showed a reduction in plasma cholesterol levels and in atherosclerotic lesions. The absence of significant reduction of plasma cholesterol levels in the context of apoE deficiency highlighted macrophage-derived apoE as key in both the regulation of plasma and tissue cholesterol levels and the progression of pre-existing lesion. Accordingly, hBcl2 expression in macrophages was associated with larger pools of Kupffer cells and Ly-6C(low) monocytes, both high producers of apoE. Additionally, increased Kupffer cells population was associated with improved clearance of apoptotic cells and modified lipoproteins.Conclusion: Collectively, these data show that promoting macrophage survival provides a supplemental source of apoE, which hinders pre-existing plaque progression.</abstract><pub>Oxford University Press (OUP)</pub><pmid>26092098</pmid><doi>10.1093/cvr/cvv177</doi></addata></record>
fulltext fulltext
identifier ISSN: 0008-6363
ispartof Cardiovascular research, 2015-09, Vol.108 (1), p.111-123
issn 0008-6363
language eng
recordid cdi_hal_primary_oai_HAL_hal_03798228v1
source Oxford University Press Journals All Titles (1996-Current)
subjects Animals
Antigens, Ly
Apolipoproteins E
Apoptosis
Atherosclerosis
Cell Survival
Cholesterol
Disease Progression
Life Sciences
Macrophages
Male
Mice
Proto-Oncogene Proteins c-bcl-2
Receptors, LDL
title Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T08%3A36%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-hal&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Promoting%20macrophage%20survival%20delays%20progression%20of%20pre-existing%20atherosclerotic%20lesions%20through%20macrophage-derived%20apoE&rft.jtitle=Cardiovascular%20research&rft.au=Bouchareychas,%20Laura&rft.date=2015-09-16&rft.volume=108&rft.issue=1&rft.spage=111&rft.epage=123&rft.pages=111-123&rft.issn=0008-6363&rft_id=info:doi/10.1093/cvr/cvv177&rft_dat=%3Chal%3Eoai_HAL_hal_03798228v1%3C/hal%3E%3Cgrp_id%3Ecdi_FETCH-hal_primary_oai_HAL_hal_03798228v13%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/26092098&rfr_iscdi=true