The effects of specific inhibitor Lp-PLA2 on vasa vasorum angiogenesis through inhibition vascular endothelial growth factor expression: study in vivo using type 2 diabetes mellitus

Insulin resistance decreases endothelin's ability to release NO, O₂, and other substances which causes inflammation and endothelial dysfunction. As a result, atherosclerotic plaques are easily formed. Hypoxia due to arterial wall thickening causes increase of vasa vasorum and HIF-1α secretion which in turn induce the production of VEGF causing angiogenesis. Darapladib is a Lp-PLA₂ inhibitor predicted to slow atherosclerosis progressivity. Experimental study used posttest with control group to Sprague Dawley, divided into 3 groups, 1) control groups, 2) type 2 diabetes mellitus group with high fat diet and 3) type 2 diabetes mellitus with high fat diet and darapladib administration. Measured parameter were glucose level, plasma insulin level, insulin resistency, lipid profile, amount of vasa vasorum and VEGF expression. One-way ANOVA test showed darapladib effect have significant differences (p<0.05) to total cholesterol lipid profile (p = 0.049), HDL (p = 0.000), LDL (p = 0.000), amount of vasa vasorum (p = 0.000), but it was not significant in VEGF expression (p = 0.375). Darapladib administration had ability to decrease lipid profile and number of vasa vasorum. However,there was no significant effect in VEGF expression. This finding was probably due to another pathway besides VEGF mediated pathway. Further studies are required to understand compensatory pathways and their effects of atherosclerotic treatment.