Elaborate evaluation of serum and tissue oxidized LDL level with darapladib therapy: A feasible diagnostic marker for early atherogenesis

Heriansyah, Teuku; Adam, Aditya Angela; Wihastuti, Titin Andri; Rohman, Mohammad Saifur

doi:10.1016/j.apjtb.2016.11.014

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…Lipid profile result from our previous publication was in line with this theory [18]. Lipid is normally stored in adipose tissue as an esterified lipid, but in high-fat diet, 40%-50% of lipid undergoes spillover causing ectopic fat deposition [23].…”

Section: Resultsmentioning

confidence: 60%

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

Wihastuti

Aini

Lutfiana

et al. 2018

TOMCJ

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Objective:This study is aimed to examine the expression of ICAM-1 and VCAM-1 in cardiac tissue of dyslipidemic Sprague Dawley rats.Methods:Eight Sprague Dawley strain rats, with 150-200 gram body weight, were divided into two groups. The control group was fed a standard diet, the positive control group was fed a high-fat diet as our previous study for 8 weeks. The pattern of distribution of ICAM-1 and VCAM-1 in cardiac muscle cell was examined by immunofluorescence and observed with a confocal laser scanning microscope. Lipid profile was also examined at the end of the study.Result:Independent t-test showed no differences in ICAM-1 and VCAM-1 expression in cardiac muscle of hypercholesterol-diet-fed Sprague Dawley rat compared to control.Conclusion:The expression of ICAM-1 and VCAM-1 in cardiac muscle did not change after the onset of atherosclerosis.

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Section: Resultsmentioning

confidence: 60%

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

Wihastuti

Aini

Lutfiana

et al. 2018

TOMCJ

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“…The animal model used in this experiment is using the combination of low doses of STZ and high-fat diet could induce metabolic syndrome mimicking human criteria (Rohman et al, 2017). This experimental has Lp-PLA 2 activity data in aortic tissue with protein/enzyme form.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidized LDL (OxLDL) has been widely demonstrated to have an important role in vascular inflammation (Zhang et al, 2013) Ox-LDL is capable of inducing monocyte adhesion to endothelial cells (Heriansyah et al, 2015). oxLDL initiates chemoattractant release, which in this way attracts macrophage migration into the lesion, and triggers the formation of reactive oxygen species (ROS), leading to oxidative stress, and the death of vascular smooth muscle cells (Heriansyah et al, 2017). Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) activity that highly correlated with oxLDL is suspected to have a significant part in atherosclerosis development and also contributes to plaque destabilization process in different pathways.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Darapladib Therapy for the Expression of Lp-PLA2 in Dyslipidemia and Type 2 Diabetes Mellitus Atherosclerosis Model

2018

japs

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Atherosclerosis is the main cause of mortality and morbidity globally. Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) activity is suspected to have a significant role in atherosclerosis. 50 Sprague-Dawley Rats were divided into five groups: normal, dyslipidemia, Type 2 diabetes mellitus (T2DM), dyslipidemia with darapladib administration and T2DM with darapladib administration. These groups were divided into two serial times: 8 and 16 weeks. mRNA Lp-PLA 2 was measured from blood and aortic tissue extraction. Aortic tissue Lp-PLA 2 was measured by immunofluorescence. Lp-PLA 2 expression in aortic tissue was consistently increased in dyslipidemia and T2DM. The expression of Lp-PLA 2 enzymatic was significantly suppressed (p < 0.05) with the administration of darapladib especially in 8 weeks groups in both dyslipidemia and T2DM. The administration of darapladib in dyslipidemia and T2DM didn't significantly suppress the expression of mRNA Lp-PLA 2 in blood and aortic tissue. The failure of genetic expression suppression of Lp-PLA 2 was found in both 8 weeks and 16 weeks groups. The expression of Lp-PLA 2 protein also showed an inclined difference between dyslipidemia and T2DM. These results showed that administration of darapladib significantly decreased Lp-PLA 2 protein but prone to increase the expression of mRNA Lp-PLA 2 in blood and aortic tissue in dyslipidemia and T2DM model.

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“…Activation of NF-kB initiates atherosclerosis process, and endothelial dysfunction is characterized by an increase in iNOS, platelet adhesion, and migration and proliferation of smooth muscle cells. Signs of inflammation may occur at any time, from the initial to the later stage of atherosclerosis development [25][26][27]. AGE may activate vascular smooth muscle cell NF-κB and mediate the migration and proliferation of smooth muscle cells [28].…”

Section: Discussionmentioning

confidence: 99%

Decreasement of Lysophosphatidylcholine Level, Nf-Kb Expression, Intima Media Thickness and Improvement of Insulin Resistance by Darapladib Treatment: In Vivo Studies of Type 2 Diabetes Mellitus Sprague-Dawley Rat Model

Wihastuti

Andiyani

Andarini

et al. 2017

Asian J Pharm Clin Res

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Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) is an enzyme with several pro-inflammatory properties that involved in pathogenesis of atherosclerosis, but some investigation shows controversial views regarding its biological role. We examined the effect of selective inhibitor of Lp-PLA 2 (darapladib) to the inflammation marker, intima-media thickness (IMT), and insulin resistance (IR) of type 2 diabetes mellitus (T2DM) rat model. This study aimed to measure lysophosphatidylcholine (lyso-PC) in serum and aortic tissue, nuclear factor kappa B (NF-κB) expression, IMT, and IR with darapladib treatment in a T2DM rat model. Methods:30 Sprague-Dawley rats were randomly divided into normal group, T2DM group and T2DM with darapladib treatment. Induction of T2DM was done by giving high-fat diet and low dose injection of streptozotocin. Blood glucose level and insulin plasma concentration were measured to calculate IR. 8 weeks and 16 weeks after treatment, we compared lyso-PC level, NF-κB expression, and IMT.Results: Darapladib significantly decreased lyso-PC level, NF-κB expression, and IMT at two serial treatments. Darapladib treatment group exhibited significant reduction of IR (0.64±0.11 vs. 2.07±0.16, at 8 weeks; and 0.93±0.08 vs. 6.48±0.55 at 16 weeks) compared with T2DM group. Conclusions:These data suggested that Lp-PLA 2 played a role in inflammation process, atherosclerosis, and IR occurring in metabolic disorder.

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Elaborate evaluation of serum and tissue oxidized LDL level with darapladib therapy: A feasible diagnostic marker for early atherogenesis

Cited by 9 publications

References 31 publications

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

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

The Effect of Darapladib Therapy for the Expression of Lp-PLA2 in Dyslipidemia and Type 2 Diabetes Mellitus Atherosclerosis Model

Decreasement of Lysophosphatidylcholine Level, Nf-Kb Expression, Intima Media Thickness and Improvement of Insulin Resistance by Darapladib Treatment: In Vivo Studies of Type 2 Diabetes Mellitus Sprague-Dawley Rat Model

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