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Ⅴ型和Ⅺα-1型胶原蛋白在人升胸主动脉瘤中的差异表达

Differential expression of collagen type V and XI alpha-1 in human ascending thoracic aortic aneurysms.

作者信息

Toumpoulis Ioannis K, Oxford Julia Thom, Cowan Douglas B, Anagnostopoulos Constantine E, Rokkas Chris K, Chamogeorgakis Themistocles P, Angouras Dimitrios C, Shemin Richard J, Navab Mohamad, Ericsson Maria, Federman Micheline, Levitsky Sidney, McCully James D

机构信息

Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.

出版信息

Ann Thorac Surg. 2009 Aug;88(2):506-13. doi: 10.1016/j.athoracsur.2009.04.030.

Abstract

BACKGROUND

The molecular mechanisms leading to ascending thoracic aortic aneurysms (ATAAs) remain unknown. We hypothesized that alterations in expression levels of specific fibrillar collagens occur during the aneurysmal process.

METHODS

Surgical samples from ascending aortas from patients with degenerative ATAAs were subdivided by aneurysm diameter: small, 5 to 6 cm; medium, 6 to 7 cm; and large, greater than 7 cm; and compared with nonaneurysmal aortas (mean diameter, 2.3 cm).

RESULTS

Histology, immunofluorescence, and electron microscopy demonstrated greater disorganization of extracellular matrix constituents in ATAAs as compared with control with an increase in collagen alpha1(XI) within regions of cystic medial degenerative lesions. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed collagens type V and alpha1(XI) were significantly and linearly increased in ATAAs as compared with control (p < 0.001). There was no change in the messenger ribonucleic acid (mRNA) expression levels of collagens type I and III. Western blot analysis showed collagens type I and III were significantly decreased and collagens alpha1(XI) and V were significantly increased and were linearly correlated with the size of the aneurysm (p < 0.001 for both).

CONCLUSIONS

These results demonstrate that increased collagen alpha1(XI) and collagen V mRNA and protein levels are linearly correlated with the size of the aneurysm and provide a potential mechanism for the generation and progression of aneurysmal enlargement.

摘要

背景

导致升主动脉瘤(ATAAs)的分子机制尚不清楚。我们推测在动脉瘤形成过程中特定纤维状胶原蛋白的表达水平会发生改变。

方法

将退行性ATAAs患者升主动脉的手术样本按动脉瘤直径进行细分:小,5至6厘米;中,6至7厘米;大,大于7厘米;并与非动脉瘤性主动脉(平均直径2.3厘米)进行比较。

结果

组织学、免疫荧光和电子显微镜检查显示,与对照组相比,ATAAs中细胞外基质成分的紊乱程度更高,囊性中层退行性病变区域内的胶原蛋白α1(XI)增加。实时定量逆转录聚合酶链反应(RT-PCR)显示,与对照组相比,ATAAs中V型胶原蛋白和α1(XI)胶原蛋白显著且呈线性增加(p < 0.001)。I型和III型胶原蛋白的信使核糖核酸(mRNA)表达水平没有变化。蛋白质印迹分析显示,I型和III型胶原蛋白显著减少,α1(XI)和V型胶原蛋白显著增加,且与动脉瘤大小呈线性相关(两者均p < 0.001)。

结论

这些结果表明,胶原蛋白α1(XI)和胶原蛋白V的mRNA及蛋白质水平增加与动脉瘤大小呈线性相关,并为动脉瘤扩大的发生和发展提供了一种潜在机制。

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