Synergistic Protective Effects Of A Statin And An Angiotensin Receptor Blocker For Initiation And Progression Of Atherosclerosis

AimAlthough 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.MethodsAtherosclerotic 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].ResultsHistological 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).ConclusionCombination 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.