Abstract 4966: The High Mobility Group AT-hook 2 Gene Plays a Crucial Role in the Development of Aortic Rupture
Introduction The high mobility group AT-hook 2 (HMGA2) gene has recently been shown to be a transcriptional organizer of transforming growth factor (TGF-β) signaling. It is proposed that HMGA2 acts in a gene-specific manner to regulate factors involved in epithelial-mesenchymal-transition (EMT), known to be expressed only during embryogenesis. We analyzed the expression profile of the HMGA2 gene in human aortic diseases.
Methods and Results Aortic specimens were collected during surgery from 51 patients (mean age 56.8±15.3), 19 patients with acute aortic dissection (type A, 14m/5f), 26 samples obtained from aortic aneurysms (14 patients showed a bicuspid aortic valve, 12 patients tricuspid aortic valve), two Marfan syndrome samples, and aortic valves. Quantitative Real-Time-polymerase chain reaction (qRT-PCR) and immunohistochemical analysis were performed. The expression of let-7 microRNA, assumed to play a role in regulation of HMGA2 in cancer cells, was quantified and measured in fetal RNA. The HMGA2 gene was highly expressed in aortic type A dissection compared with all other samples (193.1 vs 8.7 fold, p = 2,4.10−7). In fetal RNA, HMGA2 was expressed with 48-fold, however no significant expression of let-7 microRNA was detected among all investigated samples. Immunohistochemical investigation showed that HMGA2 protein was mainly detected in the endothelial cells of the vasa vasorum.
Discussion The upregulation of HMGA2 in acute aortic dissection may indicate an involvement in the pathogenesis of rupture. HMGA2 protein was mainly restricted to cells of the vasa vasorum. It seems that HMGA2-overexpression in aortic cells occurs in a let-7 independent manner, leading to increase angiogenesis of the vasa vasorum.