Atherogenesis inhibition by darapladib administration in dyslipidemia model Sprague-Dawley rats

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 A 2 (Lp-pLA 2) is an enzyme that cleaves Ox-LDL to become proatherosclerotic products. Darapladib, an Lp-pLA 2 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.

Exploration of Adhesion Molecule Expression in Cardiac Muscle of Early Atherosclerosis Dyslipidemic Sprague Dawley Rats

“…Rats were divided into two groups after acclimatization. The control group was fed a standard diet (N), the positive control group was fed a High-Fat Diet (HFD) as our previous study [16] (DL) for 8 weeks. This study was conducted at the Biomedical Laboratory and Central Laboratory of Biological Sciences, Brawijaya University after obtaining ethical clearance assessment by the Health Research Ethics Committee.…”

Darapladib Inhibit Adhesion Molecule Expression in Aorta at Early Stages of Atherosclerosis Using Sprague-Dawley Type 2 Diabetes Mellitus Model

“…There are few studies of darapladib effects in atherosclerosis. One of them is the research conducted by Heriansyah et al It showed that darapladib administration can reduce ox-LDL and foam cell amount [4]. Therefore, the aim of this study is to know darapladib effect on VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague-Dawley T2DM model.…”

“…The high prevalence of diabetes is expected to increase atherosclerosis prevalence [3]. This is because DM is a major risk factor for atherosclerosis development and clinical manifestations, including coronary artery disease, stroke, and peripheral vascular disease [4].…”

Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model

“…International Diabetes Federation (2013) have stated that there are 382 million adults (8.3%) suffering from diabetes and this number is expected to be increasing until 592 mil-lion within 25 years. The high prevalence of diabetes can increase atherosclerosis prevalence because it is a major risk factor for atherosclerosis development and clinical manifestations, including coronary artery disease, stroke, and peripheral vascular disease (Chait and Bornfeldt 2009;Heriansyah et al 2015).…”