Douglas Group: Functional coronary artery disease genetics

gillian.douglas@cardiov.ox.ac.uk

Division of Cardiovascular Medicine

Defining the function of new causal atherosclerosis genes from CAD GWAS loci using in vitro and in vivo models.

Figure showing an atherosclerotic plaque from a human coronary artery. The diameter of the lumen (left of the image) has been significantly reduced by the plaque. Within the plaque (right hand side of image) the presence of a lipid rich necrotic core are visible. A collagen rich (green staining) fibrous cap separates the plaque from the lumen of the vessel. — Figure showing an atherosclerotic plaque from a human coronary artery. The diameter of the lumen (left of the image) has been significantly reduced by the plaque. Within the plaque (right hand side of image) the presence of a lipid rich necrotic core is visible. A collagen rich (green staining) fibrous cap separates the plaque from the lumen of the vessel.

Large studies linking common variations in our genes to the occurrence of coronary artery disease have enabled us to identify several new genes that have a causative influence on the susceptibility to developing coronary artery disease, but through an unknown mechanism.

Group picture of the Functional coronary artery disease genetics research group. We use primary knockout cells in in vitro models of vascular biology eg migration, proliferation and uptake assays, to investigate the role of novel cardiovascular genes in vascular biology. We then use pathway-specific in vivo models such as murine models of vascular injury, and models of atherosclerosis progression and regression to assess the role of the novel genes in cardiovascular disease. Understanding how the these novel genes are linked with atherosclerosis and coronary artery disease will provide new information on the causes of coronary artery disease, and might identify new approaches for prevention or treatment.