Abstract 202: Synergistic Protective Effects of Statin and Angiotensin Receptor Blocker for the Progression of Atherosclerosis

Objective: Both statin and angiotensin receptor blocker (ARB) are well known to prevent the progression of atherosclerosis. However, the additive effects of anti-atherosclerosis at early period are not fully investigated. Therefore, we tried to investigate whether an anti-atherosclerotic effect of statin and ARB could be synergistic and clarify its mechanisms. Methods: Atherosclerotic plaques were developed at 23 rabbits’ iliac arteries with a high cholesterol (HC) diet and balloon inflation. We applied with 5 different treatment for 4 weeks; group 1 [n=5, HC diet]; group 2 [n=3, a regular chow diet]; group 3 [n=5, HC diet and rosuvastatin (R, 10 mg/kg)]; and group 4 [n=5, HC diet and olmesartan (O, 20 mg/kg)]; group 5 [n=5, HC diet and R + O]. End of the period, optical coherence tomography (OCT) was performed to detect the plaque characteristics and all tissues were harvested for histological evaluation. Results: Histological analysis demonstrated that atherosclerotic plaque lesions (Intima/plaque ratio, %) were decreased in the combination group compared to the statin (p=0.001) or ARB group (p=0.17). The macrophage infiltration of RAM11 staining was not significantly different between combination and each treatment group (mean±SEM=31.8±4.8% (R+O) vs. 38.1±6.53% (R), p=0.35 or 35.1±2.9% (O), p=0.62). Relative area of macrophage M1 polarization (iNOS staining) was significantly lower in the combination group compared to ARB group (3.2±0.5% (R+O) vs. 4.6 ±0.4% (R), p=0.09 or 5.2±1.0% (O), p=0.03). M2 macrophage polarization (Arg-1 staining) revealed increase in the combination group compared to each treatment group (17.7±3.0% (R+O) vs. 7.9±0.7% (R), p=0.002 or 11.9±2.8% (O), p=0.05) Conclusion: The combination of statin and ARB appeared more beneficial effects to reduce plaque formation, which may be associated with modulation of macrophage subtype in early period.