Title | Macrophage polarization and acceleration of atherosclerotic plaques in a swine model. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Lee S-G, Oh J, Bong S-K, Kim J-S, Park S, Kim S, Park S, Lee S-H, Jang Y |
Journal | PLoS One |
Volume | 13 |
Issue | 3 |
Pagination | e0193005 |
Date Published | 2018 |
ISSN | 1932-6203 |
Abstract | 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-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. RESULTS: 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. 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. |
DOI | 10.1371/journal.pone.0193005 |
Alternate Journal | PLoS ONE |
PubMed ID | 29561847 |
PubMed Central ID | PMC5862407 |
Submitted by kej2006 on June 6, 2018 - 4:13pm