Cotrufo Maurizio, Della Corte Alessandro, De Santo Luca S, Quarto Cesare, De Feo Marisa, Romano Gianpaolo, Amarelli Cristiano, Scardone Michelangelo, Di Meglio Franca, Guerra Germano, Scarano Maria, Vitale Serena, Castaldo Clotilde, Montagnani Stefania
Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Italy.
J Thorac Cardiovasc Surg. 2005 Aug;130(2):504-11. doi: 10.1016/j.jtcvs.2005.01.016.
This study aimed to assess extracellular matrix protein expression patterns at the convexity (right anterolateral wall) and the concavity of the dilated ascending aorta in patients with bicuspid aortic valve disease.
Aortic wall specimens were retrieved from the convexity and the concavity in 27 bicuspid aortic valve patients (12 with stenosis and 15 with regurgitation) and 6 heart donors (controls). Morphometry, immunohistochemistry, Western blot, and polymerase chain reaction were performed, focusing on matrix proteins involved in vascular remodeling.
Type I and III collagens were significantly decreased in bicuspid-associated dilated aortas versus controls (P < .001), particularly at the convexity (P < .05 vs concavity). Expression of messenger RNA for collagens was lower than normal only in the regurgitant subgroup. At immunohistochemistry, proteins whose overproduction has been demonstrated in response to abnormal wall stress, such as tenascin and fibronectin, were more expressed in the convexity than in the concavity, especially in the stenosis subgroup. Tenascin, which is produced by smooth muscle cells in the synthetic phenotype, was nearly undetectable in controls. Fewer smooth muscle cells (stenosis, P = .017; regurgitation, P = .008) and more severe elastic fiber fragmentation (P = .029 and P < .001) were observed in the convexity versus the concavity.
In bicuspid-associated aortic dilations, an asymmetric pattern of matrix protein expression was found that was consistent with the asymmetry in wall-stress distribution reported previously. Differences exist between patients with stenosis and those with regurgitation in terms of protein expression and content in the aortic wall. Further studies could clarify the relations between these findings and the pathogenesis of aortic dilatation in bicuspid aortic valve patients.
本研究旨在评估二叶式主动脉瓣疾病患者扩张升主动脉凸面（右前外侧壁）和凹面的细胞外基质蛋白表达模式。
从27例二叶式主动脉瓣患者（12例狭窄患者和15例反流患者）以及6例心脏供体（对照组）的升主动脉壁凸面和凹面获取标本。进行形态学测量、免疫组织化学、蛋白质印迹法和聚合酶链反应，重点关注参与血管重塑的基质蛋白。
与对照组相比，二叶式主动脉瓣相关扩张主动脉中I型和III型胶原蛋白显著减少（P <.001），尤其是在凸面（与凹面相比，P <.05）。仅在反流亚组中，胶原蛋白信使核糖核酸的表达低于正常水平。免疫组织化学显示，在异常壁应力作用下过度产生的蛋白，如腱糖蛋白和纤连蛋白，在凸面的表达高于凹面，尤其是在狭窄亚组中。在对照组中几乎检测不到由合成表型的平滑肌细胞产生的腱糖蛋白。与凹面相比，凸面观察到更少的平滑肌细胞（狭窄组，P =.017；反流组，P =.008）和更严重的弹性纤维断裂（P =.029和P <.001）。
在二叶式主动脉瓣相关的主动脉扩张中，发现了基质蛋白表达的不对称模式，这与先前报道的壁应力分布不对称一致。狭窄患者和反流患者在主动脉壁蛋白表达和含量方面存在差异。进一步的研究可以阐明这些发现与二叶式主动脉瓣患者主动脉扩张发病机制之间的关系。
