Abstract 49: Knockout of ADAMTS7, a Novel Human CAD Locus, Reduces Atherosclerosis in Both LDLR and APOE Hyperlipidemic Mouse Models

Multiple genome-wide association studies demonstrate that the genomic locus containing the gene ADAMTS7 is associated with coronary artery disease in humans. ADAMTS7 was not linked to cardiovascular disease prior to those genetic studies, and to date this association has not been validated in experimental models of atherosclerosis. An Adamts7 (Ats7) knockout mouse, with knock-in of a β-galactosidase reporter gene, was bred onto both the LDLR and APOE KO hyperlipidemic mouse models. Atherosclerosis studies were performed on the resultant Ats7/LDLR and Ats7/APOE double KO (dKO) mice and control littermates. Mice were fed western diet for 16 weeks (LDLR) or 10 weeks (APOE), and aortas and aortic roots were harvested for lesion area quantification. In addition, brachiocephalic arteries were dissected for immunohistochemical analysis of lesion composition. No differences in plasma lipids were observed between experimental groups in either study. Ats7/LDLR dKO males (N=7) and females (N=13) displayed significan...