Diagnostic and Therapeutic Strategies in Atherosclerotic Disease
Diagnostic and Therapeutic Strategies in Atherosclerotic Disease
A review of Signature patterns of gene expression in mouse atherosclerosis and their correlation to human coronary disease.
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
A collaborative effort between researchers at Stanford University and the Gladstone Institute of Cardiovascular Disease (2005) examines the gene expression signature patterns in mouse atherosclerosis and their correlation to human coronary disease. Efforts were focused at identifying central gene regulatory pathways in atherosclerotic disease and identifying classification gene sets and signatures using expression analysis. An Agilent 60-mer oligonucleotide custom-designed cardiovascular microarray allowed the extensive and systematic, large-scale rigorous identification of the underlying processes leading to disease. This study is the most comprehensive investigation of atherosclerosis gene expression patterns to date. It provides unique insights into directing diagnostic and therapeutic strategies for atherosclerotic disease.
Figure 1. Mouse atherosclerosis-related genes.
Gene selection based on a false detection rate (FDR) of < 0.05 and expression depiction by a heatmap (ordered by hierarchical clustering) demonstrates profiles that closely correlate with disease progression. The heatmap is a graphic representation of expression patterns of 6 parallel time-course studies, with time progressing (from left to right) for each of the 6 sets of strain-diet combinations used. The dominant temporal expression pattern is one that increases linearly with time (as found with 667 genes). Conversely, fewer genes (64 total) reveal the opposite (decreasing) temporal pattern.
Figure 2. Expression of mouse atherosclerosis-related genes in human coronary artery disease.
40 human coronary artery samples, with and without atherosclerotic lesions, were used to investigate expression profiles of those differentially-regulated mouse genes previously identified. Atherosclerosis-associated mouse genes were matched to human orthologs/homologs by gene symbol and known homology (Homologene, No. 396). Their expression was compared in human atherosclerotic plaques classified as lesion vs. no lesion based on a significance analysis of microarrays (SAM) FDR of < 0.025. Expression of top genes is represented graphically as a heatmap, where rows represent row-normalized expression of each gene and columns represent coronary artery samples.
Title: Signature patterns of gene expression in mouse atherosclerosis and their correlation to human coronary disease.
Authors: Wagner RA, Ashley EA, King JY, Ferrara R, Spin JM, Sanan DA, Narasimhan B, Tibshirani R, Tsao PS, Efron B, Quertermous T.
Journal: Physiol Genomics. 2005 Jul 14;22(2):213-26.
More