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

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• 作者：Teuku Heriansyah¹ ; Aditya Angela Adam² ; Titin Andri Wihastuti² ; ^{wihastuti.fk@ub.ac.id} ; Mohammad Saifur Rohman³
• 关键词：OxLDL ; Serum ; Aorta ; Lp-PLA2 ; Darapladib ; Foam cell
• 刊名：Asian Pacific Journal of Tropical Biomedicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：7
• 期：2
• 页码：134-138
• 全文大小：682 K
• 卷排序：7

文摘

To compare oxidized low density lipoprotein (oxLDL) levels in serum and vascular wall of Sprague-Dawley rats, identify their patterns in 8 weeks and 16 weeks of dyslipidemia induced by high fat diet, compare foam cells in aorta of each group and investigate lipoprotein-associated phospholipase A2 (Lp-PLA2) role in atherosclerosis by darapladib administration.MethodsThis study generated in twenty-four Sprague-Dawley rats. Rats were divided into 6 groups, which were received normal diet (normal group), high fat diet and high fat diet plus darapladib therapy for both 8 weeks and 16 weeks. Surgeries were performed at Week 8 and Week 16 to take the blood serum and aortic tissue. Level of oxLDL in serum, oxLDL aortic tissue, foam cell amount in aortic tissue, and Lp-PLA2 expression in aortic tissue were measured.ResultsThere were significant differences in oxLDL level in serum, aortic tissue and foam cell amount (P < 0.05). There was no significant difference in Lp-PLA2 expression in aortic tissue. OxLDL in serum and aortic tissue had a very strong correlation (r2 > 0.9, P < 0.05). This study also composed an equation for oxLDL level in aortic tissue prediction. Factorial ANOVA found that there was a significant difference of oxLDL level in the interactions between duration and location, location and treatment, and also duration, location and treatment (P < 0.01). Administration of darapladib was able to reduce levels of oxLDL in serum, aortic tissue and foam cell significantly (P < 0.05, P < 0.05 and P < 0.01, subsequently).ConclusionsOxLDL level is location-dependent and duration-dependent. As a feasible early diagnosis, we can predict oxLDL level in aortic tissue by its level in serum. Though Lp-PLA2 expression was unsignificant, Lp-PLA2 inhibition by darapladib can reduce oxidative stress and inflammation in atherogenesis.