Schmid Franz-Xaver, Bielenberg Katrin, Holmer Stephan, Lehle Karla, Djavidani Behrus, Prasser Christopher, Wiesenack Christoph, Birnbaum Dietrich
Department of Cardiothoracic and Vascular Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany.
Eur J Cardiothorac Surg. 2004 May;25(5):748-53. doi: 10.1016/j.ejcts.2004.02.028.
A higher incidence of pulmonary autograft dilatation is assumed in patients with ascending aortic dilatation and bicuspid aortic valve disease. To examine whether structural abnormalities are present in the ascending aorta as well as in the pulmonary trunk (PT) we specifically addressed molecular mechanisms and signalling pathways for aneurysm formation in ascending aortic aneurysms and PT of patients with different aortic valve pathology undergoing an extended Ross procedure.
Wall segments resected from aortic aneurysms (20 patients, 7 bicuspid aortic valves BAV, and 13 tricuspid aortic valves TAV) and from PTs were submitted to analysis of leukocyte infiltration (immunohistochemistry), smooth muscle cell (SMC) apoptosis (in situ end-labelling of DNA-fragments TUNEL), and expression of death-promoting proteins perforin, granzyme B, Fas/FasL (immunoblotting).
Degenerative changes including rarefication and apoptosis of SMCs were significantly more severe in BAV than TAV disease (apoptotic index 9.2+/-3.2 vs. 11.9+/-6.2, P = 0.02). Immunohistochemistry confirmed presence and activation of death-promoting mediators in aneurysmal tissue whereas pulmonary tissue displayed only few apoptotic cells, occasional Fas+cells, rarely colocalized with FasL. By Western blot analysis extracts from BAV and TAV but not pulmonary artery wall contained appreciable amounts of perforin, granzyme B, and Fas/FasL.
Aneurysm formation is associated with SMC apoptosis and local signal expression of activated cells in patients with bicuspid as well as TAV. The PT itself is not pathologically involved with only minor degenerative changes. Although the disease process in the aorta appeared to be more severe in patients with BAV, there was similarity of histological and molecular changes of the pulmonary artery wall in all patients. Dilation of the pulmonary autograft seems not to be the result of histopathological and biomolecular mechanisms in the PT.
升主动脉扩张和二叶式主动脉瓣疾病患者的肺动脉自体移植扩张发生率较高。为了研究升主动脉和肺动脉干（PT）是否存在结构异常，我们专门探讨了接受扩大Ross手术的不同主动脉瓣病变患者的升主动脉瘤和PT中动脉瘤形成的分子机制和信号通路。
从主动脉瘤（20例患者，7例二叶式主动脉瓣BAV，13例三叶式主动脉瓣TAV）和PT切除的壁段进行白细胞浸润分析（免疫组织化学）、平滑肌细胞（SMC）凋亡分析（DNA片段原位末端标记TUNEL）以及促死亡蛋白穿孔素、颗粒酶B、Fas/FasL的表达分析（免疫印迹）。
BAV疾病中SMC的退行性改变包括稀疏和凋亡比TAV疾病显著更严重（凋亡指数9.2±3.2对11.9±6.2，P = 0.02）。免疫组织化学证实动脉瘤组织中存在并激活了促死亡介质，而肺组织仅显示少量凋亡细胞，偶尔有Fas+细胞，很少与FasL共定位。通过蛋白质免疫印迹分析，BAV和TAV的提取物中含有可观量的穿孔素颗粒酶B和Fas/FasL，但肺动脉壁提取物中没有。
二叶式主动脉瓣和三叶式主动脉瓣患者的动脉瘤形成与SMC凋亡和活化细胞的局部信号表达有关。PT本身仅存在轻微退行性改变，无病理参与。虽然BAV患者的主动脉疾病过程似乎更严重，但所有患者肺动脉壁的组织学和分子变化具有相似性。肺动脉自体移植扩张似乎不是PT中组织病理学和生物分子机制的结果。
