Background: Type 2 Diabetes Melitus (T2DM) is a condition of insulin resistance that causes extensive tissue damage due to vascular inflammation and oxidative stress. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has anti-inflammatory role as it hydrolyzes atherogenesis mediators such as oxidized LDL (Ox LDL) and platelet activating factor (PAF) but in contrast, it has pro inflammatory effect as it produced lysophosphatidylcholine (lysoPC) and oxidized fatty acid (oxFA). Methods and Results: This study aimed to measure inflammation marker of T2DM in vivo model with Lp-PLA2 selective inhibitor (darapladib) treatment. It used true experimental laboratory and post test only with control group design using 30 spraque dowley rats that is divided into 3 main groups: normal, T2DM, and T2DM with darapladib (DMDP) administration group. Each group are divided into 2 serial treatment times: 8-weeks and 16-weeks intervention. So, there are 6 groups total with 5 rat in each group. Parameter measured was ox-LDL, tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6), PAF, perivascular adipose tissue (PAT) thickness and also blood glucose, lipid profile, and insulin plasma level. ANOVA test result showed that darapladib were significantly (p: 0.000) lowering tissue and blood ox-LDL level, iNOS, PAF, IL-6 and PAT thickness on T2DM in vivo model. Conclusions: Darapladib proved to have anti inflammation role on T2DM model.

Objective: Hyperglycemia and hyperlipidemia in diabetes mellitus (DM) can lead an atherosclerosis. The increase of low-density lipoprotein level in DM and atherosclerosis is correlated with lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). Lp-PLA 2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids. LysoPC regulated inflammation mediators, include cytokines, adhesion molecules (such as vascular cell adhesion molecule-1 [VCAM-1] and intercellular adhesion molecules-1 [ICAM-1]), and monocyte chemoattractant protein-1 (MCP-1) chemotactic. Darapladib is known as a Lp-PLA 2 specific inhibitor. It is also considered to be an atherosclerosis treatment. 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 Type 2 DM (T2DM) model. Methods:About 30 Spraque-Dawley rats are divided into three main groups: Normal, T2DM, and T2DM with darapladib administration group. Each group consists of 2 serials treatment time: 8 and 16 weeks treatment group. Fasting blood glucose, resistance insulin, and lipid profile were measured and analyzed to ensure T2DM model. VCAM-1 and ICAM-1 expression were measured using double staining immunofluorescence. Each data were analyzed using one-way ANOVA.Results: There is a significant difference in VCAM-1 expression in T2DM group (8 and 16 weeks), with p=0.011 and 0.034 (p<0.05), respectively. Mean while, a significant difference for ICAM-1 only showed in 8 weeks T2DM group with p=0.03 (p<0.05). Moreover, there is a decreasing trend in 16 weeks T2DM group. Conclusion:Our results showed that darapladib can decrease VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using SpragueDawley T2DM model. This showed another evidence of darapladib as atherosclerosis treatment.