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December 4, 2009

Researchers Uncover Gene Module behind Atherosclerosis

  • Scientists at Karolinska Institutet identified a network of 128 genes that is important for the recruitment of white blood cells into the atherosclerotic plaque. The findings suggest that the severity of atherosclerosis depends on the rate of migration of white blood cells from the blood into the atherosclerotic plaques. Although this pathway is already known to play a role in atherosclerosis, the study revealed that it is the rate-limiting step for disease progression.

    The results are published in PLoS Genetics in a paper titled “Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2; The Stockholm Atherosclerosis Gene Expression (STAGE) Study.”

    The scientists along with a team at Washington University, Seattle performed whole-genome expression analyses in several organs to identify functionally associated genes important for coronary artery disease (CAD) development. They found an atherosclerosis module (A-module) consisting of 128 genes, enriched with genetic risk for CAD, involving transendothelial migration of leukocytes and LIM domain binding 2 (LDB2) as its high-hierarchy regulator.

    The involvement of most of these genes in CAD was not previously known, but it was understood that they are involved in endothelial function and angiogenesis. The exact roles of all 128 genes in atherogenesis remain unexplained, however. Future studies will focus on understanding the details of how these genes actually contribute to atherosclerosis in cell cultures and animal models.


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