Abstract 11570: Targeted Disruption of JCAD/KIAA1462, a Coronary Artery Disease-associated Gene Product, Inhibits Angiogenic Processes in Vitro and in Vivo

Background: Recent genome-wide association studies newly identified the human KIAA1462 gene as a new locus for coronary artery disease. However, the function of the gene product, named JCAD (junctional protein associated with coronary artery disease), is unknown. Because JCAD is expressed at cell-cell junctions in endothelial cells, we hypothesized and tested whether JCAD regulates angiogenic processes in vitro and in vivo. Methods and Results: Cell culture experiments revealed impaired angiogenic ability (WST-1 assay, wound healing, and tube formation) by the knock down of JCAD with siRNA (p<0.05 vs. control siRNA). We generated mice lacking JCAD (JCAD-/-) by gene-targeted deletion of JCAD to address in vivo angiogenic function. JCAD-/- mice did not show differences in development of retinal vasculature. Ex vivo aortic ring model demonstrated impaired neovascularization in aorta from JCAD-/- mice than control wild-type mice (p<0.05). Tumor growth was assessed by monitoring tumor volume after the subcutan...