The effect of darapladib therapy for the expression of Lp-PLA2 in dyslipidemia and type 2 diabetes mellitus atherosclerosis model

Abstract

Atherosclerosis is the main cause of mortality and morbidity globally. Lipoprotein-associated phospholipase A2 (Lp-PLA2) 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-PLA2 was measured from blood and aortic tissue extraction. Aortic tissue Lp-PLA2 was measured by immunofluorescence. Lp- PLA2 expression in aortic tissue was consistently increased in dyslipidemia and T2DM. The expression of Lp- PLA2 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-PLA2 in blood and aortic tissue. The failure of genetic expression suppression of Lp-PLA2 was found in both 8 weeks and 16 weeks groups. The expression of Lp-PLA2 protein also showed an inclined difference between dyslipidemia and T2DM. These results showed that administration of darapladib significantly decreased Lp-PLA2 protein but prone to increase the expression of mRNA Lp-PLA2 in blood and aortic tissue in dyslipidemia and T2DM model.