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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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.

Original languageEnglish
Article numbere0215604
JournalPloS one
Volume14
Issue number5
DOIs
Publication statusPublished - 2019 May 3

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Lee, S. G., Lee, S. J., Thuy, N. V. P., Kim, J. S., Lee, J. J., Lee, O. H., Kim, C. K., Oh, J., Park, S., Lee, O. H., Kim, S. H., Park, S., Lee, S. H., Hong, S. J., Ahn, C. M., Kim, B. K., Ko, Y. G., Choi, D., Hong, M. K., & Jang, Y. (2019). Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis. PloS one, 14(5), [e0215604]. https://doi.org/10.1371/JOURNAL.PONE.0215604