Abstract

Background: Atherosclerosis is a chronic inflammation disease that is caused by the interaction between monocyte and endothelial injury in tunica intima. One of the major factor of atherosclerosis is dyslipidemia. Chronic dyslipidemia, especially hypercholesterolemia, can directly alter endothelial cell through reactive oxygen species (ROS) production that oxidizes low-density lipoprotein (LDL) to become oxidized LDL (Ox-LDL). Proinflammatory cytokines, the products of perivascular adipocyte tissue (PVAT), may draw macrophage. Macrophage then engulfs Ox-LDL and becomes foam cell within tunica intima. Lipoprotein-associated phospholipase A2 (Lp-pLA2) is an enzyme that cleaves Ox-LDL to become proatherosclerotic products. Darapladib, an Lp-pLA2 inhibitor, is expected to inhibit atherosclerotic lesion progressivity.

Aims and Objective: To know the effects of darapladib on Ox-LDL level, PVAT thickness, and foam cell number.

Materials and Methods: This study used in vivo posttest controlled group design with two time series. Thirty male Sprague–Dawley rats divided into two group based on time series (8 weeks and 16 weeks). Each time serial was divided into three groups which were: standard diet group ;high-fat diet group; and dyslipidemia model with darapladib administration group with dose of 200 mg/200 g body weight (BW). The parameters that was measured in this study were lipid profile [total cholesterol, LDL/very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL)], Ox-LDL level, number of foam cells, and PVAT thickness.

Result: Ox-LDL level and foam cell number decreased significantly (p = 0.000 and p = 0.005, respectively), while PVAT thickness did not show significant difference (p = 0.912).

Conclusion: In this, study, it has been proven that darapladib decreases Ox-LDL levels and foam cell numbers but not in PVAT thickness, even though a decreasing pattern was observed histologically. Further study needed to know the optimum dosage of darapladib administration.

Key words: Darapladib; Lp-PLA2; Ox-LDL; Foam Cell; PVAT; Dyslipidemia