Absi Tarek S, Sundt Thoralf M, Tung William S, Moon Marc, Lee Jason K, Damiano Ralph R, Thompson Robert W
Departments of Surgery, Sections of Cardiac and Vascular Surgery, Washington University School of Medicine, 9901 Wohl Hospital, 4960 Children's Place, St. Louis, MO 63110, USA.
J Thorac Cardiovasc Surg. 2003 Aug;126(2):344-57; discission 357. doi: 10.1016/s0022-5223(02)73576-9.
The purpose of this study was to profile altered patterns of gene expression that characterize degenerative ascending thoracic aortic aneurysms and to compare these patterns with those observed for infrarenal abdominal aortic aneurysms.
Full-thickness aortic wall tissues were obtained during surgical repair of degenerative thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms (n = 4 each), with normal thoracic and abdominal aortas from organ transplant donors used as control preparations. Radiolabeled complementary DNA was prepared for each specimen and hybridized to complementary DNA microarrays, and differential levels of gene expression between aneurysmal and normal aortic tissues at each site were assessed by parametric statistics.
Of 1185 genes examined, 112 (9.5%) were differentially expressed (P <.05) between thoracic aortic aneurysms and normal thoracic aorta, with 105 increased and 7 decreased. There were 104 genes (8.8%) differentially expressed between infrarenal abdominal aortic aneurysms and normal abdominal aorta (65 increased and 39 decreased). Quantitative increases in expression for 97 genes were unique to thoracic aortic aneurysms, whereas increases for 61 genes were unique to infrarenal abdominal aortic aneurysms. Although 8 gene products were significantly altered in both thoracic and infrarenal abdominal aortic aneurysms, these changes were directionally concordant for only 4 (matrix metalloproteinase 9/gelatinase B, v-yes-1 oncogene, mitogen-activated protein kinase 9, and intercellular adhesion molecule 1/CD54). Results for 9 genes were independently confirmed by quantitative reverse transcriptase-polymerase chain reaction.
Thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms exhibit distinct patterns of gene expression relative to normal aorta from the same sites, with most alterations being unique to each disease. Degenerative aneurysms arising in different locations are thus characterized by a high degree of molecular heterogeneity, reflecting different pathophysiologic mechanisms.
本研究旨在剖析退行性升主动脉瘤所特有的基因表达改变模式，并将这些模式与肾下腹主动脉瘤所观察到的模式进行比较。
在退行性胸主动脉瘤和肾下腹主动脉瘤（各4例）的手术修复过程中获取全层主动脉壁组织，将来自器官移植供体的正常胸主动脉和腹主动脉用作对照样本。为每个样本制备放射性标记的互补DNA，并与互补DNA微阵列杂交，通过参数统计评估每个部位动脉瘤性主动脉组织与正常主动脉组织之间基因表达的差异水平。
在检测的1185个基因中，胸主动脉瘤与正常胸主动脉之间有112个基因（9.5%）差异表达（P <.05），其中105个基因表达增加，7个基因表达减少。肾下腹主动脉瘤与正常腹主动脉之间有104个基因（8.8%）差异表达（65个基因表达增加，39个基因表达减少）。97个基因的表达定量增加是胸主动脉瘤所特有的，而61个基因的增加是肾下腹主动脉瘤所特有的。虽然8种基因产物在胸主动脉瘤和肾下腹主动脉瘤中均有显著改变，但只有4种（基质金属蛋白酶9/明胶酶B、v-yes-1癌基因、丝裂原活化蛋白激酶9和细胞间黏附分子1/CD54）的这些变化在方向上是一致的。9个基因的结果通过定量逆转录聚合酶链反应得到独立验证。
相对于相同部位的正常主动脉，胸主动脉瘤和肾下腹主动脉瘤表现出不同的基因表达模式，大多数改变是每种疾病所特有的。因此，不同部位发生的退行性动脉瘤具有高度的分子异质性，反映了不同的病理生理机制。
