Differential gene expression in human abdominal aorta: Aneurysmal versus occlusive disease

Peter J. Armstrong, Jason M. Johanning, William C. Gallon, Jason R. Delatore, David P. Franklin, David C. Han, David J. Carey, James R. Elmore

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Objective: Inflammation and atherosclerosis are present in both abdominal aortic aneurysm (AAA) and arterial occlusive disease (AOD). Changes in gene expression that underlie the development of AAA versus AOD are poorly defined. This study evaluated differences in gene expression in AAA, AOD, and control aortic tissue with human gene array technology. Methods: RNA was isolated from human aortic specimens (seven AAA, five AOD, and five control), and complementary DNA (cDNA) probes were generated. The cDNA probes were hybridized to a human cell interaction array of 265 genes and quantitated with phosphorimaging. The data were corrected for background and were standardized to house-keeping genes. Statistical differences in individual gene expression were determined with the Kruskal-Wallis test. Results: Of 265 genes studied, 11 showed statistically different expression in diseased aorta as compared with control. The following three genes were downregulated in AAA: collagen VI α-(P < .037), glycoprotein IIIA (P < .006), and α2- macroglobulin (P < .020). The following two genes were upregulated in AOD: laminin α4 (P < .034) and insulin-like growth factor 2 receptor (P < .049). The following three genes were upregulated in both AAA and AOD: matrix metalloproteinase-9 (MMP-9; P < .005), intercellular adhesion molecule-1 (P < .012), and tumor necrosis factor-β receptor (P < .022). The following three genes were downregulated in both AAA and AOD: integrin α5 (P < .012), ephrin AS (P < .037), and rho/rac guanine nucleotide exchange factor (P < .028). Of 16 MMPs evaluated, only MMP-9 was significantly (P < .005) upregulated in both AAA and AOD. Evaluation results of four tissue inhibitors of metalloproteinases showed no significant difference in expression for all tissue types, although tissue inhibitor of metalloproteinase-1 trended toward upregulation in AAA (P = .053). Eight of the fifteen most highly expressed genes in all the groups were extracellular matrix or secreted proteins. Of these, only collagen VI α-(P < .037) showed a significant change, although biglycan trended toward downregulation in AAA (P = .076). Conclusion: This study used cDNA array technology in the comparison of human control and pathologic aortic tissue. Six genes had similar differential expression in both AAA and AOD as compared with control. Even more interesting were differences between AAA and AOD in the expression of five genes. These data suggest a similarity in genetic expression for both AAA and AOD, with altered expression of several genes playing a role in disease differentiation.

Original languageEnglish (US)
Pages (from-to)346-355
Number of pages10
JournalJournal of vascular surgery
Volume35
Issue number2
DOIs
StatePublished - Feb 2002

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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