Sarpogrelate and atorvastatin synergistically ameliorate hyperlipidemia-induced aortic damage in LDL receptor deficient (LDL-R⁻/⁻) mice

Abstract

Hyperlipidemia is a major risk factor for blood vessel damage, which can lead to cardiovascular diseases. Statins are the first-line treatment for hyperlipidemia and atherosclerosis. However, most patients receiving statins do not reach the low-density lipoprotein-cholesterol (LDL-c) goal. Sarpogrelate (SP) has been shown to reduce blood lipids and oxidative stress. Therefore, this study investigated the effects of SP plus atorvastatin compared to atorvastatin alone on aortic damage in LDL-R^⁻/⁻ mice with hyperlipidemia. Male LDL-R^⁻/⁻ mice were randomly divided into four groups: normal diet-fed mice (control group), high-cholesterol diet-fed mice (H group), high-cholesterol diet-fed mice treated with atorvastatin (HA group), and high-cholesterol diet-fed mice treated with atorvastatin + SP (HAS group). Total cholesterol (TC) and LDL-c levels were lower in the HA and HAS groups. SP plus atorvastatin was more effective in reducing TC and LDL-c levels, compared to atorvastatin alone. Morphological and immunohistochemical analyses showed that lipid deposition and macrophage infiltration were significantly suppressed in the HAS group, compared to those in the HA group. CD36 expression was lower in aotra tissues of mice in the HA and HAS groups than in the H group. Furthermore, macrophages and pro-inflammatory cytokine levels were lower in the HA and HAS groups than in the H group. There were significant differences in macrophages, pro-inflammatory cytokine and CD36 levels between HA and HAS groups. Therefore, SP plus atorvastatin might be more effective in ameliorating hyperlipidemia-induced aortic damage in LDL-R^⁻/⁻ mice, compared to atorvastatin alone.