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

• Published in: Asian Pacific Journal of Tropical Biomedicine
• Main Authors: Teuku Heriansyah, Aditya Angela Adam, Titin Andri Wihastuti, Mohammad Saifur Rohman
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wolters Kluwer Medknow Publications 2017
• Subjects: OxLDL; Serum; Aorta; Lp-PLA2; Darapladib; Foam cell; Arctic medicine. Tropical medicine; RC955-962; Biology (General); QH301-705.5; Arctic
• Online Access: https://doi.org/10.1016/j.apjtb.2016.11.014; https://doaj.org/article/ad67c055c1d4413f8b9e93c1941065c5

Objective: 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. Methods: This 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. Results: There 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). Conclusions: OxLDL 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.