Macrophage polarization and acceleration of atherosclerotic plaques in a swine model.

Atherosclerosis is a well-known cause of cardiovascular disease and is associated with a variety of inflammatory reactions. However, an adequate large-animal model of advanced plaques to investigate the pathophysiology of atherosclerosis is lacking. Therefore, we developed and assessed a swine model...

Full description

Bibliographic Details
Main Authors: Seul-Gee Lee, Jaewon Oh, Sung-Kyung Bong, Jung-Sun Kim, Seil Park, Sehoon Kim, Sungha Park, Sang-Hak Lee, Yangsoo Jang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5862407?pdf=render
_version_ 1818965743234973696
author Seul-Gee Lee
Jaewon Oh
Sung-Kyung Bong
Jung-Sun Kim
Seil Park
Sehoon Kim
Sungha Park
Sang-Hak Lee
Yangsoo Jang
author_facet Seul-Gee Lee
Jaewon Oh
Sung-Kyung Bong
Jung-Sun Kim
Seil Park
Sehoon Kim
Sungha Park
Sang-Hak Lee
Yangsoo Jang
author_sort Seul-Gee Lee
collection DOAJ
description Atherosclerosis is a well-known cause of cardiovascular disease and is associated with a variety of inflammatory reactions. However, an adequate large-animal model of advanced plaques to investigate the pathophysiology of atherosclerosis is lacking. Therefore, we developed and assessed a swine model of advanced atherosclerotic plaques with macrophage polarization.Mini-pigs were fed a 2% high-cholesterol diet for 7 weeks followed by withdrawal periods of 4 weeks. Endothelial denudation was performed using a balloon catheter on 32 coronary and femoral arteries of 8 mini-pigs. Inflammatory proteins (high-mobility group box 1 [HMGB1] or tumor necrosis factor alpha (TNF-α) were injected via a micro-infusion catheter into the vessel wall. All lesions were assessed with angiography and optical coherence tomography and all tissues were harvested for histological evaluation.Intima/plaque area was significantly higher in the HMGB1- and TNF-α-injected groups compared to the saline-injected group (p = 0.002). CD68 antibody detection and polarization of M1 macrophages significantly increased in the inflammatory protein-injected groups (p<0.001). In addition, advanced atherosclerotic plaques were observed more in the inflammatory protein-injected groups compared with the control upon histologic evaluation.Direct injection of inflammatory proteins was associated with acceleration of atherosclerotic plaque formation with M1 macrophage polarization. Therefore, direct delivery of inflammatory proteins may induce a pro-inflammatory response, providing a possible strategy for development of an advanced atherosclerotic large-animal model in a relatively short time period.
first_indexed 2024-12-20T13:21:51Z
format Article
id doaj.art-db81ffdfc8904a51ab294ef531499297
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-20T13:21:51Z
publishDate 2018-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-db81ffdfc8904a51ab294ef5314992972022-12-21T19:39:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019300510.1371/journal.pone.0193005Macrophage polarization and acceleration of atherosclerotic plaques in a swine model.Seul-Gee LeeJaewon OhSung-Kyung BongJung-Sun KimSeil ParkSehoon KimSungha ParkSang-Hak LeeYangsoo JangAtherosclerosis is a well-known cause of cardiovascular disease and is associated with a variety of inflammatory reactions. However, an adequate large-animal model of advanced plaques to investigate the pathophysiology of atherosclerosis is lacking. Therefore, we developed and assessed a swine model of advanced atherosclerotic plaques with macrophage polarization.Mini-pigs were fed a 2% high-cholesterol diet for 7 weeks followed by withdrawal periods of 4 weeks. Endothelial denudation was performed using a balloon catheter on 32 coronary and femoral arteries of 8 mini-pigs. Inflammatory proteins (high-mobility group box 1 [HMGB1] or tumor necrosis factor alpha (TNF-α) were injected via a micro-infusion catheter into the vessel wall. All lesions were assessed with angiography and optical coherence tomography and all tissues were harvested for histological evaluation.Intima/plaque area was significantly higher in the HMGB1- and TNF-α-injected groups compared to the saline-injected group (p = 0.002). CD68 antibody detection and polarization of M1 macrophages significantly increased in the inflammatory protein-injected groups (p<0.001). In addition, advanced atherosclerotic plaques were observed more in the inflammatory protein-injected groups compared with the control upon histologic evaluation.Direct injection of inflammatory proteins was associated with acceleration of atherosclerotic plaque formation with M1 macrophage polarization. Therefore, direct delivery of inflammatory proteins may induce a pro-inflammatory response, providing a possible strategy for development of an advanced atherosclerotic large-animal model in a relatively short time period.http://europepmc.org/articles/PMC5862407?pdf=render
spellingShingle Seul-Gee Lee
Jaewon Oh
Sung-Kyung Bong
Jung-Sun Kim
Seil Park
Sehoon Kim
Sungha Park
Sang-Hak Lee
Yangsoo Jang
Macrophage polarization and acceleration of atherosclerotic plaques in a swine model.
PLoS ONE
title Macrophage polarization and acceleration of atherosclerotic plaques in a swine model.
title_full Macrophage polarization and acceleration of atherosclerotic plaques in a swine model.
title_fullStr Macrophage polarization and acceleration of atherosclerotic plaques in a swine model.
title_full_unstemmed Macrophage polarization and acceleration of atherosclerotic plaques in a swine model.
title_short Macrophage polarization and acceleration of atherosclerotic plaques in a swine model.
title_sort macrophage polarization and acceleration of atherosclerotic plaques in a swine model
url http://europepmc.org/articles/PMC5862407?pdf=render
work_keys_str_mv AT seulgeelee macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel
AT jaewonoh macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel
AT sungkyungbong macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel
AT jungsunkim macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel
AT seilpark macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel
AT sehoonkim macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel
AT sunghapark macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel
AT sanghaklee macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel
AT yangsoojang macrophagepolarizationandaccelerationofatheroscleroticplaquesinaswinemodel