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

Research output: Contribution to journalArticle

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
Pages (from-to)e0215604
JournalPloS one
Volume14
Issue number5
DOIs
Publication statusPublished - 2019 Jan 1

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
angiotensins
angiotensin II
Angiotensin Receptor Antagonists
atherosclerosis
protective effect
Atherosclerosis
Nutrition
high fat diet
receptors
Macrophages
Diet
Cholesterol
macrophages
Atherosclerotic Plaques
rabbits
Rabbits
inflation
additive effect
Balloons

All Science Journal Classification (ASJC) codes

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

Cite this

Lee, Seul Gee ; Lee, Seung Jun ; Thuy, Nguyen Viet Phuong ; Kim, Jung Sun ; Lee, Jung Jae ; Lee, Oh Hyun ; Kim, Choong Ki ; Oh, Jaewon ; Park, Seil ; Lee, Ok Hee ; Kim, Se Hoon ; Park, Sungha ; Lee, Sang Hak ; Hong, Sung Jin ; Ahn, Chul Min ; Kim, Byeong Keuk ; Ko, Young Guk ; Choi, Donghoon ; Hong, Myeong Ki ; Jang, Yangsoo. / Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis. In: PloS one. 2019 ; Vol. 14, No. 5. pp. e0215604.
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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.",
author = "Lee, {Seul Gee} and Lee, {Seung Jun} and Thuy, {Nguyen Viet Phuong} and Kim, {Jung Sun} and Lee, {Jung Jae} and Lee, {Oh Hyun} and Kim, {Choong Ki} and Jaewon Oh and Seil Park and Lee, {Ok Hee} and Kim, {Se Hoon} and Sungha Park and Lee, {Sang Hak} and Hong, {Sung Jin} and Ahn, {Chul Min} and Kim, {Byeong Keuk} and Ko, {Young Guk} and Donghoon Choi and Hong, {Myeong Ki} and Yangsoo Jang",
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Lee, SG, Lee, SJ, Thuy, NVP, Kim, JS, Lee, JJ, Lee, OH, Kim, CK, Oh, J, Park, S, Lee, OH, Kim, SH, Park, S, Lee, SH, Hong, SJ, Ahn, CM, Kim, BK, Ko, YG, Choi, D, Hong, MK & Jang, Y 2019, 'Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis', PloS one, vol. 14, no. 5, pp. e0215604. https://doi.org/10.1371/journal.pone.0215604

Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis. / Lee, Seul Gee; Lee, Seung Jun; Thuy, Nguyen Viet Phuong; Kim, Jung Sun; Lee, Jung Jae; Lee, Oh Hyun; Kim, Choong Ki; Oh, Jaewon; Park, Seil; Lee, Ok Hee; Kim, Se Hoon; Park, Sungha; Lee, Sang Hak; Hong, Sung Jin; Ahn, Chul Min; Kim, Byeong Keuk; Ko, Young Guk; Choi, Donghoon; Hong, Myeong Ki; Jang, Yangsoo.

In: PloS one, Vol. 14, No. 5, 01.01.2019, p. e0215604.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis

AU - Lee, Seul Gee

AU - Lee, Seung Jun

AU - Thuy, Nguyen Viet Phuong

AU - Kim, Jung Sun

AU - Lee, Jung Jae

AU - Lee, Oh Hyun

AU - Kim, Choong Ki

AU - Oh, Jaewon

AU - Park, Seil

AU - Lee, Ok Hee

AU - Kim, Se Hoon

AU - Park, Sungha

AU - Lee, Sang Hak

AU - Hong, Sung Jin

AU - Ahn, Chul Min

AU - Kim, Byeong Keuk

AU - Ko, Young Guk

AU - Choi, Donghoon

AU - Hong, Myeong Ki

AU - Jang, Yangsoo

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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