ABSTRACT
PURPOSE: Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. MATERIALS AND METHODS: Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg.kg-1.d-1) and high-dose darapladib (50 mg.kg-1.d-1) interventions were then administered over the course of 2 weeks. RESULTS: The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p0.05). CONCLUSION: Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.
Subject(s)
Animals , Male , Rats , 1-Alkyl-2-acetylglycerophosphocholine Esterase/antagonists & inhibitors , Atherosclerosis/blood , Benzaldehydes , C-Reactive Protein/metabolism , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dose-Response Relationship, Drug , Oximes , Phospholipase A2 Inhibitors/administration & dosage , Rats, Sprague-Dawley , Triglycerides/blood , rho-Associated Kinases/metabolismABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects of small interference RNA (siRNA) on epidermal growth factor-like domain 7 (egfl7) gene expression in human endothelial cell line HUVEC.</p><p><b>METHODS</b>siRNA targeting egfl7 (siRNA1, siRNA2, siRNA3 and siRNA4) was constructed through online design of Amnion company and transfected into human endothelial cell line HUVEC with lipofectamine. The nontransfected cells and cells treated with control siRNA were taken as controls. At 24, 48 and 72 hours post various interventions, cell viability was determined by MTS method as well as LDH and ATP releasing tests. egfl7 expressions at protein and mRNA levels were detected by Western blot and RT-PCR respectively.</p><p><b>RESULTS</b>Cell survival rate, LDH and ATP release were significantly reduced in siRNA treated cells compared to control cells (P < 0.05). Similarly, egfl7 expression at protein and mRNA levels was also significantly reduced in siRNA treated cells (P < 0.01), especially in siRNA1 treated cells.</p><p><b>CONCLUSION</b>siRNA inhibited egfl7 gene expression and cell survival in HUVEC.</p>