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

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13 Citations (Scopus)


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.

Original languageEnglish
Article numbere0215604
JournalPloS one
Issue number5
Publication statusPublished - 2019 May 3

Bibliographical note

Funding Information:
Funding: This study was supported by grants from the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2017R1A2B2003191), the Ministry of Science and ICT (2017M3A9E9073585), the Daewoong Pharmaceutical Company and the Cardiovascular Research Center (Seoul, Korea) to JSK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2019 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

All Science Journal Classification (ASJC) codes

  • General


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