Abstract 19809: Heparin Binding EGF-Like Growth Factor (HB-EGF) is a Novel Regulator for Hyperlipidemia
Objective: Elevation of ApoB-containing lipoproteins in circulation a well-established risk factor for the development of cardiovascular diseases. HB-EGF, which is an endogenous ligand of EGFR and ERBB4, was reported to be positively associated with blood lipid level in human individuals. In this study, we tested the effects of HB-EGF targeting on the induction of hyperlipidemia and hyperlipidemia-induced vascular diseases atherosclerosis and aneurysm in a mouse model.
Methods and Results: LDLR deficient mice were fed a high fat diet (HFD, 21% fat and 0.2% cholesterol) throughout the study for the induction of hyperlipidemia and atherosclerosis. For aneurysm study, we added 28-day of angiotensin II infusion (1,000ng/kg/min) via osmotic mini-pump installation as a final step. For HB-EGF targeting, the mice were injected intraperitoneally with control or HB-EGF antisense oligonucleotide (ASO) for 12 weeks. At termination step, we measured lipid concentrations in circulation, aortic lesion size, and thoracic and abdominal aortic diameters. First, we detected that the HB-EGF targeting induced remarkable suppression of circulating lipid levels with VLDL the most suppressed (Figure attached). Second, the HB-EGF ASO targeting efficiently protected against atherosclerosis and aneurysm in the aorta. Third, the HB-EGF ASO administration induced significant lipid accumulation in the liver.
Conclusion: Current results indicate that HB-EGF is a key regulator for the induction of hyperlipidemia. Liver-associated phenotypes suggest that HB-EGF appear to mediate VLDL secretion from the liver into circulation.
Author Disclosures: S. Lee: None. R. Lee: None. M. Graham: None. D. Rateri: None. R. Temel: None. A.J. Lusis: None. J.A. Berliner: None.
- © 2016 by American Heart Association, Inc.