Published on:April 2017
    Journal of Cardiovascular Disease Research, 2017; 8(2):xx-xx
    Original Article | doi:10.5530/jcdr.2017.2.xx

    Lowering Inflammation Level by Lp-PLA2 Inhibitor (Darapladib) in Early Atherosclerosis Development: in vivo Rat Type 2 Diabetes Mellitus Model

    Authors:

    Heriansyah Teuku,1 Wihastuti Titin Andri,2 Bambang Budi Siswanto,3 Anwar Santoso,3 Renan Sukmawan,3 Djanggan Sargowo, 4 Imam Subekti,5 Aulanni’am,6 Nurjati Chairani Siregar,7 Saptawati Bordosono8

    1Department of Cardiology and Vascular Medicine, Faculty of Medicine, Syiah Kuala University, Banda Aceh, Indonesia. 23111

    2Department of Biomedicine, Faculty of Medicine, Brawijaya University, Malang, Indonesia. 65145

    3Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. 16424

    4Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Brawijaya, Malang, Indonesia. 65145

    5Department of Internal Medicine, Division of Metabolic and Endocrinology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. 16424

    6Department of Biochemistry, Faculty of Veterinary Medicine, University of Brawijaya, Malang, Indonesia. 65145

    7Department of Pathology Anatomy, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. 16424

    8Department of Nutrition, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. 16424

    Abstract:

    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.

    Key words: Type 2 diabetes mellitus, Inflammation, Oxidative stress, Lipoprotein-associated phospholipase A2, Darapladib.