Defining the role of the CAD gene JCAD in vascular remodelling

JCAD is a novel gene, identified by GWAS as associated with coronary artery disease (CAD).

In our current BHF project grant we found that Jcad alters atherosclerotic plaque formation, specifically related to areas of disturbed blood flow.

Using an in vitro cell based assay in primary endothelial cells we confirmed a role for JCAD in the endothelial cell shear stress mechanotransduction pathway.

Our studies establish a clear role for the new CAD gene JCAD in vascular pathophysiology, via shear stress mechanotransduction pathways.

We now propose to investigate the specific role of endothelial cell JCAD in flow-responsive vascular pathophysiology, and test its potential as a therapeutic target.

To address this objective we will investigate endothelial cell-specific effects of JCAD in both physiological and pathological vascular remodelling in models of exercise training and hind limb ischemia, respectively.