Microarray analysis of human abdominal aortic aneurysm (AAA) detected altered gene expression profiles including H19

Abstract

Abstract AAA is often a life-threatening disease with poorly understood pathogenesis. We examined gene expression profiles between AAA and normal aorta specimens by cDNA microarray analysis. AAA wall specimens from 5 patients with AAA and grossly normal aortic walls from 3 transplant donors were employed in this study. Total RNA was extracted from each specimen, RT into cDNA, and labeled with phosphorus α-32P. cDNA probes were then hybridized onto human cardiovascular microarray and analyzed by densitometry. Quantitative differences of some genes were further explored by SYBR green-mediated qRT-PCR analysis. Pairwise comparisons of both microarray and qRT-PCR results were made by Student t-test. Most of the 588 genes studied had similar expression among AAA specimens and control aortas, however, 25 genes were upregulated and 26 downregulated. Expression of MMP-9, TIMP3, collagen 1A1 (COL1A1), COL6A3, COL15A1, decorin, MCP 1, Apo E, Apo D, H19 and others was increased. Expression of COL4A4, biglycan, caveolin 3, galectin 1, LDL receptor-related protein 1, extracellular SOD 3, ANP receptor A precursor and others was decreased. Most qRT-PCR results agreed well with those from microarray analysis, with few exceptions. A number of genes that have been previously postulated to participate in AAA pathogenesis, have been upregulated or their expression has been altered. We also revealed some genes that have not been yet studied in human AAA. Of note, H19, one of the most highly up-regulated transcripts in two mouse aneurysm models, was also significantly upregulated in human AAA. These results indicate that many genes involved in different cellular functions might contribute to the pathogenesis of AAA. Supported in part by grant RO1 HL64340 from NIH.