Macrophage polarization and acceleration of atherosclerotic plaques in a swine model

• Published in: PloS one Vol. 13; no. 3; p. e0193005
• Main Authors: Lee, Seul-Gee, Oh, Jaewon, Bong, Sung-Kyung, Kim, Jung-Sun, Park, Seil, Kim, Sehoon, Park, Sungha, Lee, Sang-Hak, Jang, Yangsoo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.03.2018; Public Library of Science (PLoS)
• Subjects: Acceleration; Angiography; Apoptosis; Arteries; Arteriosclerosis; Atherosclerosis; Atherosclerotic plaque; Balloon catheters; Biology and Life Sciences; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Denudation; Development and progression; Evaluation; Femoral artery; Femur; Health aspects; High cholesterol diet; HMGB1 protein; Hogs; Hospitals; Inflammation; Inflammatory response; Laboratory animals; Lesions; Livestock; Macrophages; Medical imaging; Medical instruments; Medicine; Medicine and Health Sciences; Optical Coherence Tomography; Physicians; Physiological aspects; Plaques; Polarity (Biology); Polarization; Proteins; Research and Analysis Methods; Smooth muscle; Swine; Thrombosis; Tissues; Tomography; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Veins & arteries
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0193005

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.