Novel pathways in the pathobiology of human abdominal aortic aneurysms.
OBJECTIVE
Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs.


METHODS
A custom-designed 'AAA-chip' was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta. Protein analyses were performed on selected genes.


RESULTS
Altogether 38 of the 43 genes on the 'AAA-chip' showed significantly different expression. Novel validated genes in AAA pathobiology included ADCY7, ARL4C, BLNK, FOSB, GATM, LYZ, MFGE8, PRUNE2, PTPRC, SMTN, TMODI and TPM2. These genes represent a wide range of biological functions, such as calcium signaling, development and differentiation, as well as cell adhesion not previously implicated in AAA pathobiology. Protein analyses for GATM, CD4, CXCR4, BLNK, PLEK, LYZ, FOSB, DUSP6, ITGA5 and PTPRC confirmed the mRNA findings.


CONCLUSIONS
The results provide new directions for future research into AAA pathogenesis to study the role of novel genes confirmed here. New treatments and diagnostic tools for AAA could potentially be identified by studying these novel pathways.
Department of Visceral, Thoracic and Vascular Surgery, Technical University of Dresden, Dresden, Germany.
Irene
I
Hinterseher
Robert
R
Erdman
James R
JR
Elmore
Elizabeth
E
Stahl
Matthew C
MC
Pahl
Kimberly
K
Derr
Alicia
A
Golden
John H
JH
Lillvis
Matthew C
MC
Cindric
Kathryn
K
Jackson
William D
WD
Bowen
Charles M
CM
Schworer
Michael A
MA
Chernousov
David P
DP
Franklin
John L
JL
Gray
Robert P
RP
Garvin
Zoran
Z
Gatalica
David J
DJ
Carey
Gerard
G
Tromp
Helena
H
Kuivaniemi
D000368:Aged; D000906:Antibodies; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D020013:Calcium Signaling / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D058262:Receptor Activity-Modifying Protein 1 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D000906:Antibodies; C545502:RAMP1 protein, human; D012333:RNA, Messenger; D058262:Receptor Activity-Modifying Protein 1; D019255:NADPH Oxidases; C113333:NCF4 protein, human