Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.
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Cited by: 32


The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression. We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007). Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.

MeSH terms

Aged, 80 and over
Aorta, Abdominal
Aorta, Thoracic
Aortic Aneurysm, Abdominal
Child, Preschool
Endothelial Cells
Gene Expression Regulation, Developmental
Genes, Homeobox
Genetic Association Studies
Homeodomain Proteins
Middle Aged
Myocytes, Smooth Muscle
RNA, Messenger
Transcription Factors
Young Adult


Lillvis, John H
Erdman, Robert
Schworer, Charles M
Golden, Alicia
Derr, Kimberly
Gatalica, Zoran
Cox, Laura A
Shen, Jianbin
Vander Heide, Richard S
Lenk, Guy M
Hlavaty, Leigh
Li, Li
Elmore, James R
Franklin, David P
Gray, John L
Garvin, Robert P
Carey, David J
Lancaster, Wayne D
Tromp, Gerard
Kuivaniemi, Helena

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