Differential gene expression in human abdominal aorta: aneurysmal versus occlusive disease.
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 housekeeping 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 alpha1 (P <.037), glycoprotein IIIA (P <.006), and alpha2-macroglobulin (P <.020). The following two genes were upregulated in AOD: laminin alpha4 (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--beta receptor (P <.022). The following three genes were downregulated in both AAA and AOD: integrin alpha5 (P <.012), ephrin A5 (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 alpha1 (P <.037) showed a significant change, although biglycan trended toward downregulation in AAA (P =.076).


CONCLUSIONS
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.
Armstrong
Peter J
PJ
Section of Vascular Surgery, Sigfried and Janet Weis Center for Research, Geisinger Medical Center, Danville, PA 17822-2150, USA.
Johanning
Jason M
JM
Calton
William C
WC
Delatore
Jason R
JR
Franklin
David P
DP
Han
David C
DC
Carey
David J
DJ
Elmore
James R
JR
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D001012:Aorta, Abdominal / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000235:genetics; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000235:genetics; D024142:Collagen Type VI / Q000235:genetics; D036386:Ephrin-A5; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D005796:Genes / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D039482:Integrin alpha5; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007797:Laminin / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D017527:Receptor, IGF Type 2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D000511:alpha-Macroglobulins / Q000235:genetics
D015703:Antigens, CD; D024142:Collagen Type VI; D036386:Ephrin-A5; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D020662:Guanine Nucleotide Exchange Factors; D039482:Integrin alpha5; C501369:LAMA4 protein, human; D007797:Laminin; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D017527:Receptor, IGF Type 2; D019715:Tissue Inhibitor of Metalloproteinase-1; D000511:alpha-Macroglobulins; D018799:Intercellular Adhesion Molecule-1; D020782:Matrix Metalloproteinases