Abstract 358: Targeting of Heparin Binding EGF-like Growth Factor (HB-EGF) Efficiently Inhibits Atherosclerosis

Objective: Heparin-binding EGF-like growth factor (HB-EGF) is a receptor ligand that regulates inflammatory gene expression in the human aortic endothelial cells. In this study, we examined the effects of targeting HB-EGF using an antisense oligonucleotide (ASO) in the development of atherosclerosis. Methods and Results: Control and HB-EGF ASOs were injected intraperitoneally (i.p.; weekly; Dose: 50 mg/kg/wk) for 12 weeks into LDLR deficient mice fed a fat-enriched diet (21% fat; 0.2% cholesterol). Compared with the control ASO injected group (N=13), the HB-EGF ASO injected group (N=15) had efficiently reduced atherosclerosis in the arch of aorta (p<0.0001). The HB-EGF ASO also significantly reduced plasma cholesterol concentration (p = 0.0397). We observed that the VLDL was consistently reduced in all HB-EGF ASO injected mice tested. In liver tissue, the HB-EGF ASO induced significant downregulation of gene expressions of the sterol synthetic pathway as determined by a microarray and DAVID functional ana...