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ABSTRACT: Background
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.Results
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-? (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007).Conclusions
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.
SUBMITTER: Lillvis JH
PROVIDER: S-EPMC3125234 | biostudies-literature | 2011 May
REPOSITORIES: biostudies-literature
Lillvis John H JH Erdman Robert R Schworer Charles M CM Golden Alicia A Derr Kimberly K Gatalica Zoran Z Cox Laura A LA Shen Jianbin J Vander Heide Richard S RS Lenk Guy M GM Hlavaty Leigh L Li Li L Elmore James R JR Franklin David P DP Gray John L JL Garvin Robert P RP Carey David J DJ Lancaster Wayne D WD Tromp Gerard G Kuivaniemi Helena H
BMC physiology 20110531
<h4>Background</h4>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.<h4>Results</h4>We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibi ...[more]