Lesauskaite V, Tanganelli P, Sassi C, Neri E, Diciolla F, Ivanoviene L, Epistolato M C, Lalinga A V, Alessandrini C, Spina D
Institute of Cardiology and Department of Biochemistry, Kaunas University of Medicine, Lithuania.
Hum Pathol. 2001 Sep;32(9):1003-11. doi: 10.1053/hupa.2001.27107.
The etiopathogenesis of thoracic aortic aneurysms is currently an issue of debate. The present study investigated ultrastructural, morphometric, and immunohistochemical aspects of smooth muscle cells (SMCs) in chronic aneurysm of the thoracic aorta (aneurysm group), aortic dilatation associated with valvular disease (valvular group), and dissection of the thoracic aorta (dissection group). Fragments of the ascending aorta that had been taken from the patients during coronary bypass surgery were used as controls. No significant difference was observed in the density of SMCs between the 3 pathologic groups put together and the controls. Only separate analysis of SMC density in each of the pathologic groups showed that the valvular group samples had significantly smaller amounts of SMCs in the internal layer of the media than the dissection group samples and controls. Ultrastructural analysis, in situ end labeling, propidium iodide assay, and DNA laddering did not show apoptosis of SMCs in the samples investigated. Ultrastructure of SMCs characteristic of the synthetic phenotype, together with increased expression of osteopontin in the media of pathologic thoracic aortas indicated the transition of SMCs from the contractile to the synthetic phenotype. Immunohistochemical investigation showed that medial SMCs in the samples taken from aortas of all 3 pathologic groups expressed stronger immunoreactivity for matrix metalloproteinase 1, 2, and 9 and tissue inhibitor of metalloproteinase 1 and 2 than the controls. The present study shows that during the formation of aneurysms, dissection of the thoracic aorta, or aortic dilatation associated with valvular disease, loss of SMCs was not of great importance with respect to their transition from the contractile to the synthetic type in leading to increased production of matrix metalloproteinases.
胸主动脉瘤的发病机制目前仍是一个有争议的问题。本研究调查了胸主动脉慢性动脉瘤（动脉瘤组）、与瓣膜疾病相关的主动脉扩张（瓣膜组）和胸主动脉夹层（夹层组）中平滑肌细胞（SMC）的超微结构、形态计量学和免疫组织化学方面。在冠状动脉搭桥手术期间从患者身上获取的升主动脉片段用作对照。将这3个病理组与对照组放在一起比较，SMC的密度没有显著差异。只有对每个病理组的SMC密度进行单独分析时才发现，瓣膜组样本中中膜内层的SMC数量明显少于夹层组样本和对照组。超微结构分析、原位末端标记、碘化丙啶检测和DNA梯状条带分析均未显示所研究样本中的SMC发生凋亡。病理胸主动脉中膜具有合成表型特征的SMC超微结构，以及骨桥蛋白表达增加，表明SMC从收缩表型转变为合成表型。免疫组织化学研究表明，与对照组相比，取自所有3个病理组主动脉的样本中的中膜SMC对基质金属蛋白酶1、2和9以及金属蛋白酶组织抑制剂1和2表现出更强的免疫反应性。本研究表明，在动脉瘤形成、胸主动脉夹层或与瓣膜疾病相关的主动脉扩张过程中，SMC数量的减少对于其从收缩型转变为合成型从而导致基质金属蛋白酶产生增加来说并不重要。
