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

 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 
 PLOS ONE, Vol.14(5) : e0215604, 2019 
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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.
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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
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