Cystic medial degeneration of the aorta is associated with p53 accumulation, Bax upregulation, apoptotic cell death, and cell proliferation
Cystic medial degeneration of the aorta is associated with p53 accumulation, Bax upregulation, apoptotic cell death, and cell proliferation
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DOI：
10.1136/hrt.82.3.286
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发表时间：
1999-09-01
期刊：
影响因子：
5.7
通讯作者：
Schaefer, HE
中科院分区：
文献类型：
--
作者：
Ihling, C;Szombathy, T;Schaefer, HE
为探讨p53、Bc 12相关蛋白X（Bax）和细胞凋亡在主动脉囊状中层变性（CMD）过程中与细胞更新相关的作用，采用组织化学、免疫组织化学、生物化学和形态计量学方法，结果免疫组织化学染色显示在所有标本中26.1（11.5）%的血管平滑肌细胞（VSMCs）中存在p53-IR（对照组0.8（1.3）%; p < 0.001）。在所有标本中，10%（5.4%）的中膜细胞中存在β-IR（对照组为0.3%（0.5%）; p < 0.001）。内侧VSMC（α-肌动蛋白阳性），细胞质染色为凋亡特异性蛋白（c-jun/ASP）在20/20例标本中存在（0.7（0.6）%的VSMC，对照组0%，p < 0.001），而末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）阳性VSMC存在于17/20份标本中（1（1.5）%的VSMC，对照0%，p < 0.001）。通过电子显微镜和琼脂糖凝胶电泳后寡核小体DNA片段的显示证实了细胞凋亡的存在。如双标记和连续切片的研究所示，p53-IR、c-jun-IR、c-jun/ASP-IR和阳性TUNEL标记定位于主动脉中膜的相同隔室，提高了p53和Bax在CMD期间触发VSMC凋亡中的可能作用。MIB 1/Ki-67阳性中膜VSMC（α-肌动蛋白阳性）和间充质细胞（波形蛋白阳性）存在于所有标本中（中膜细胞的2.5（2.8）%;对照0.3（0.9）%，p < 0.001），主要在血管周围区域，表明细胞。再生过程中CMD可能主要来自周围的vasa vasorum. Conclusion，这项研究表明，CMD的正式发病机制的特点是由p53积累，Bax上调，细胞凋亡，和细胞再生的细胞死亡。然而，p53激活和Bax上调的精确刺激以及p53和细胞凋亡在解剖过程本身中的作用仍然难以捉摸。
Objective-To address a potential role for p53, Bc12 associated protein X (Bax), and apoptosis in the processes associated with cell turnover during cystic medial degeneration (CMD) of the aorta,Methods-Histochemical, immunohistochemical, biochemical, and morphometric methods were used to assess the presence and distribution of p53 immunoreactivity (p53-IR) and Bax immunoreactivity (Bax-IR), as well as the presence of apoptosis and tissue repair processes.Results-Immunohistochemical staining disclosed evidence for p53-IR in all specimens in 26.1 (11.5)% of vascular smooth muscle cells (VSMCs) (controls 0.8 (1.3)%; p < 0.001). Bax-IR was present in all specimens in 10 (5.4)% of medial cells (controls 0.3 (0.5)%; p < 0.001). Medial VSMCs (a-actin positive) with cytoplasmic staining for an apoptosis specific protein (c-jun/ASP) were present in 20/20 specimens (0.7 (0.6)% of VSMCs, controls 0%, p < 0.001), whereas terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) positive VSMCs were present in 17/20 specimens (1 (1.5)% of VSMCs,controls 0%, p < 0.001). The presence of apoptosis was confirmed by electron microscopy and the demonstration of oligonucleosomal DNA fragments after agarose gel electrophoresis. As shown by double labeling and investigation of serial sections, p53-IR, Bax-IR, c-jun/ASP-IR, and positive TUNEL labeling localised to the same compartments of the aortic media, raising a possible role for p53 and Bax in the triggering of apoptosis of VSMC during CMD. MIB1/Ki-67 positive medial VSMCs (a-actin positive) and mesenchymal cells (vimentin positive) were present in all specimens (2.5 (2.8)% of medial cells; controls 0.3 (0.9)%, p < 0.001) mainly in the region around the vasa vasorum, indicating that cell. regeneration during CMD may originate mainly from the mesenchyme surrounding the vasa vasorum.Conclusion-This study shows that the formal pathogenesis of CMD is characterised by p53 accumulation, Bax upregulation, cell death by apoptosis, and cell regeneration. Nevertheless, the precise stimuli of p53 activation and Bax upregulation as well as the role of p53 and apoptosis in the dissection process itself remain elusive.