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Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis

Authors
 Seul-Gee Lee  ;  Seung-Jun Lee  ;  Nguyen Viet Phuong Thuy  ;  Jung-Sun Kim  ;  Jung-Jae Lee  ;  Oh-Hyun Lee  ;  Choong-Ki Kim  ;  Jaewon Oh  ;  Seil Park  ;  Ok-Hee Lee  ;  Se Hoon Kim  ;  Sungha Park  ;  Sang-Hak Lee  ;  Sung-Jin Hong  ;  Chul-Min Ahn  ;  Byeong-Keuk Kim  ;  Young-Guk Ko  ;  Donghoon Choi  ;  Myeong-Ki Hong  ;  Yangsoo Jang 
Citation
 PLOS ONE, Vol.14(5) : e0215604, 2019 
Journal Title
 PLOS ONE 
Issue Date
2019
Abstract
AIM: Although the atheroprotective effects of statins and angiotensin II receptor blockers (ARBs) are well-established, little is known about their additive effects, especially during the early period of atherosclerosis. The aim of this study was to investigate whether combination of a statin and an ARB exerts synergistic anti-atherosclerotic effects, and to elucidate the mechanisms of combined effects. METHODS: Atherosclerotic plaques were developed in arteries of 23 rabbits using a high-cholesterol diet (HCD) and intra-arterial balloon inflation. Rabbits received one of five different treatment strategies for 4 weeks: positive control [n = 5, HCD]; negative control [n = 3, regular chow diet]; statin [n = 5, HCD and rosuvastatin 10 mg]; ARB [n = 5, HCD and olmesartan 20 mg]; and combination [n = 5, HCD and statin+ARB]. RESULTS: Histological analysis demonstrated that development of atherosclerotic plaques was inhibited more in combination group than in statin group (P = 0.001). Although macrophage infiltration identified by RAM11 staining was not significantly different between combination and individual treatment groups (31.76±4.84% [combination] vs. 38.11±6.53% [statin; P = 0.35] or 35.14±2.87% [ARB; P = 0.62]), the relative proportion of pro-inflammatory M1-macrophages was significantly lower in combination group than in ARB group (3.20±0.47% vs. 5.20±0.78%, P = 0.02). Furthermore, M2-macrophage polarization was higher in combination group than in statin group (17.70±3.04% vs. 7.86±0.68%, P = 0.001). CONCLUSION: Combination treatment with a statin and an ARB produced synergistic protective effects for atherosclerosis initiation and progression, which may be attributed to modulation of macrophage characteristics in the early period of atherosclerosis.
Files in This Item:
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DOI
10.1371/journal.pone.0215604
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Oh Hyun(이오현) ORCID logo https://orcid.org/0000-0001-7070-7720
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
Hong, Myeong Ki(홍명기) ORCID logo https://orcid.org/0000-0002-2090-2031
Hong, Sung Jin(홍성진) ORCID logo https://orcid.org/0000-0003-4893-039X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/169567
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