%0 Journal Article
%T Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms
%A John H Lillvis
%A Robert Erdman
%A Charles M Schworer
%A Alicia Golden
%A Kimberly Derr
%A Zoran Gatalica
%A Laura A Cox
%A Jianbin Shen
%A Richard S Vander Heide
%A Guy M Lenk
%A Leigh Hlavaty
%A Li Li
%A James R Elmore
%A David P Franklin
%A John L Gray
%A Robert P Garvin
%A David J Carey
%A Wayne D Lancaster
%A Gerard Tromp
%A Helena Kuivaniemi
%J BMC Physiology
%D 2011
%I BioMed Central
%R 10.1186/1472-6793-11-9
%X 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-¦Ã (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.Many vascular diseases have the tendency to manifest at specific sites in the vasculature. Aortic aneurysms are one such disease with approximately 90% developing between the renal arteries and iliac bifurcation. Aneurysms develop less frequently in the ascending and descending thoracic aorta, and are distinct from abdominal aortic aneurysms (AAAs) in prevalence, risk factors, genetics and histology [1].Several intrinsic structural differences between the abdominal and thoracic aorta may contribute to aneurysm susceptibility [2,3]. The abdominal aorta has a narrower diameter and contains several major branch points, both of which result in turbulent blood flow and decreased shear stress. Areas of low shear stress are more susceptible to atherosclerotic lesions. In addition, the abdominal aortic wall is thinner than that of the thoracic aorta, conta
%U http://www.biomedcentral.com/1472-6793/11/9