From Hairballs to an Understanding of Transendothelial Migration of Monocytes in Atherosclerosis
In the current issue of ATVB, Shang et al provide compelling evidence for the involvement of LIM domain binding 2 (LDB2) in the transendothelial migration of monocytes in atherosclerosis.1 The article is also of interest because of the systems analyses that led to its identification as a strong candidate.
See accompanying article on page 2068
LDB2 was identified earlier as a key driver of atherosclerosis based on studies of gene expression profiles of tissues obtained from patients.2 Using samples from the Stockholm Atherosclerosis Gene Expression (STAGE) study, the authors profiled gene expression of 5 atherosclerosis-relevant tissues from 114 patients undergoing coronary artery bypass grafting. The tissues collected were distal internal mammary artery, wall of the ascending aorta at the aortic root, anterior hepatic edge, skeletal muscle, and visceral fat. A total of 278 gene expression profiles were used in a coupled 2-way clustering analysis3 to identify 60 gene subnetworks in these tissues. Two of the gene clusters, one in atherosclerotic arterial wall (49 genes) and the other in visceral fat (59 genes), segregated the patients according to the extent of atherosclerosis as measured by quantitative coronary angiography. The authors further validated their findings using expression data obtained from carotid lesions isolated from patients undergoing carotid stenosis surgery. Clustering of data identified 8 gene subnetworks in carotid lesions, one of which segregated the patients according to the extent of atherosclerosis as measured by ultrasound-measured intima-media thickness. …