Phenotypic modulation of smooth muscle cells in human cerebral aneurysmal walls

脑动脉瘤的生长和破裂机制尚不清楚。我们用免疫组织化学方法来确定表型调制的平滑肌细胞（SMCs）在脑动脉瘤的生长和破裂中的作用。材料与方法：在手术或尸检时获得动脉瘤壁标本（N=58），并在尸检时获得12条对照脑动脉。用α -平滑肌肌动蛋白（α -SMA）、结蛋白、平滑肌肌球蛋白重链亚型（SM 1、SM 2和SMemb）、巨噬细胞和调节SMemb基因诱导的碱性转录调节结合蛋白2（BTEB 2）的抗体对半脑切片进行免疫组织化学染色。在对照脑动脉中，中膜SMC对α -SMA、结蛋白、SM 1和SM 2免疫染色强烈;对SMemb免疫反应微弱。未破裂动脉瘤和破裂动脉瘤平滑肌细胞均未见结蛋白表达，α -SMA表达保持良好，30%未破裂动脉瘤SMemb表达增强，而所有破裂动脉瘤SM 2和SMemb表达均降低。BTEB 2的表达在巨噬细胞和平滑肌细胞中增加，在大到未破裂的动脉瘤中：在破裂的动脉瘤中没有观察到巨噬细胞浸润。我们的研究表明，平滑肌细胞在血管壁的表型不同的收缩型在正常脑动脉中膜。在一些未破裂的动脉瘤中，至少有一些SMC是合成型的。BTEB 2在巨噬细胞和平滑肌细胞中的表达上调可能与细胞的生长有关。破裂动脉瘤中的SMC可能在破裂前失去了两种表型（收缩型和合成型）。

The growth and rupture mechanisms of cerebral aneurysms are still unknown. We used immunohistochemical methods to determine the role of phenotypically modulated smooth muscle cells (SMCs) in the growth and rupture of cerebral aneurysms. Materials and Methods : Aneurysmal wall specimens (N=58) were obtained at operation or autopsy, and 12 control cerebral arteries were obtained at autopsy. Semiserial sections were subjected to immunohistochemical staining with antibodies to α -smooth muscle actin (α -SMA), desmin, smooth muscle myosin heavy chain isoforms (SM1 , SM2 and SMemb), macrophages and basic transcription regulatory binding protein 2 (BTEB2) which regulates the induction of the gene for SMemb. In control cerebral arteries, SMCs in the media was strongly immunostained for α -SMA, desmin, SM1 and SM2 ; immunoreactivity for SMemb was faint. SMCs in both unruptured and ruptured aneurysmal walls showed no staining of desmin; the expression of α -SMA was well preserved, the expression of SMemb was increased in 30 % of unruptured aneurysms, although the expression of SM2 and SMemb was decreased in all ruptured aneurysms. The expression of BTEB2 was increased in macrophages and SMCs in the large to grant unruptured aneurysms: it was not seen in ruptured aneurysms exhibiting macrophage infiltration. Our study suggests that SMCs in aneurysmal walls are phenotypically different from the contractile type in the media of normal cerebral arteries. In some unruptured aneurysms, at least some SMCs are of the synthetic type. The up-regulation of BTEB2 in macrophages and SMCs appears to the related to aneurysmal growth. SMCs in ruptured aneurysms may have lost both phenotypes (contractyle and synthetic) before rupture.