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Macrophage polarization and acceleration of atherosclerotic plaques in a swine model

 Seul-Gee Lee  ;  Jaewon Oh  ;  Sung-Kyung Bong  ;  Jung-Sun Kim  ;  Seil Park  ;  Sehoon Kim  ;  Sungha Park  ;  Sang-Hak Lee  ;  Yangsoo Jang 
 PLoS One, Vol.13(3) : e0193005, 2018 
Journal Title
 PLoS One 
Issue Date
Animals ; Atherosclerosis/*metabolism/pathology ; Animal Disease Models ; HMGB1 Protein/*metabolism ; Macrophages/*metabolism/pathology ; Atherosclerotic/*metabolism/pathology Plaque ; Swine ; Miniature Swine ; Tumor Necrosis Factor-alpha/*metabolism ; Tunica Intima/*metabolism/pathology
AIMS: 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. METHODS: 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-alpha) 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. RESULTS: Intima/plaque area was significantly higher in the HMGB1- and TNF-alpha-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. CONCLUSION: 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.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김세훈(Kim, Se Hoon) ORCID logo https://orcid.org/0000-0001-7516-7372
김중선(Kim, Jung Sun) ORCID logo https://orcid.org/0000-0003-2263-3274
박성하(Park, Sung Ha) ORCID logo https://orcid.org/0000-0001-5362-478X
오재원(Oh, Jae Won) ORCID logo https://orcid.org/0000-0002-4585-1488
이상학(Lee, Sang Hak) ORCID logo https://orcid.org/0000-0002-4535-3745
장양수(Jang, Yang Soo) ORCID logo https://orcid.org/0000-0002-2169-3112
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