Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.
Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.
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DOI：
10.1186/1472-6793-11-9
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发表时间：
2011-05-31
期刊：
影响因子：
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通讯作者：
Kuivaniemi H
中科院分区：
文献类型：
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作者：
Lillvis JH;Erdman R;Schworer CM;Golden A;Derr K;Gatalica Z;Cox LA;Shen J;Vander Heide RS;Lenk GM;Hlavaty L;Li L;Elmore JR;Franklin DP;Gray JL;Garvin RP;Carey DJ;Lancaster WD;Tromp G;Kuivaniemi H
肾下腹主动脉相对于其他主动脉区域表现出更高的疾病易感性。同种异体移植研究交换胸部和腹部节段表明，区域的敏感性保持无论位置，提示胚胎起源，组织成分和位点特异性基因表达的实质性作用。我们分析了基因表达的微阵列在狒狒arctas，并发现HOX基因家族的成员表现出空间表达差异。选择HOXA 4进行进一步研究，因为与胸主动脉相比，其在腹主动脉中的表达降低。Western blot分析显示，24例人乳腺癌组织中HOXA 4蛋白水平显著高于腹部组织（P < 0.001）。HOXA 4免疫组化染色显示主动脉内皮细胞和平滑肌细胞的核和核周染色。与年龄匹配的非腹主动脉瘤对照组相比，人类腹主动脉瘤（AAA）中HOXA 4转录水平显著降低（P < 0.00004）。INF-γ（AAA发病机制中的重要炎性细胞因子）刺激培养的人主动脉内皮细胞和平滑肌细胞显示HOXA 4蛋白水平降低（P < 0.0007）。我们的研究结果表明，HOXA 4在人类腹主动脉瘤中表达的空间变异持续到成年期，HOXA 4表达的下调与AAAs相关，AAAs是老年人群的一种重要的主动脉疾病。
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.