Apoptosis and overexpression of Bax protein and bax mRNA in smooth muscle cells within intimal hyperplasia of human radial arteries -: Analysis with arteriovenous fistulas used for hemodialysis
Apoptosis and overexpression of Bax protein and bax mRNA in smooth muscle cells within intimal hyperplasia of human radial arteries -: Analysis with arteriovenous fistulas used for hemodialysis
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DOI：
10.1161/01.atv.19.9.2066
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发表时间：
1999-09-01
影响因子：
8.7
通讯作者：
Fujiwara, H
中科院分区：
文献类型：
--
作者：
Hayakawa, Y;Takemura, G;Fujiwara, H
有一种类型的动脉硬化伴中型动脉重塑，其中平滑肌细胞（SMC）的内膜增生起主要作用，巨噬细胞、T淋巴细胞和泡沫细胞很少。还不清楚细胞凋亡和细胞凋亡诱导剂Bax的表达是否根据这种类型的人动脉硬化的进展而增加，这与所谓的动脉粥样硬化不同，Bax与细胞凋亡抑制剂Bcl-2异二聚化，Bax与Bcl-2的比率决定细胞凋亡或存活。因此，我们研究了细胞凋亡和Bax，bax mRNA和Bcl-2在用于血液透析的人动静脉（AV）内瘘中的表达，AV内瘘是上述类型动脉硬化的代表。材料为20例接受AV分流术的慢性肾功能衰竭患者的20支桡动脉。SMC，巨噬细胞，和T淋巴细胞在光镜（LM）水平进行化学鉴定。采用原位末端脱氧核苷酸转移酶（TdT）介导的地高辛-dUTP缺口末端标记法（TUNEL）在光镜和电镜水平检测细胞凋亡。增殖细胞核抗原（PCNA）检测细胞增殖活性，免疫组化和Western blot检测Bax和Bcl-2的表达。原位杂交检测bax mRNA的表达，LM TUNEL阳性细胞在内膜和中膜均随血管狭窄程度的增加而明显增加。电镜分析显示，在合成型和收缩型SMC中均可见凋亡的超微结构。狭窄>50%的血管内膜和中膜的发生率高于狭窄>50%的血管内膜和中膜。
There is a type of arteriosclerosis with remodeling of middle-size arteries in which intimal hyperplasia of smooth muscle cells (SMCs) plays the main role, and there are few macrophages, T lymphocytes, and foam cells. It is unknown whether apoptosis and the expression of Bax, an inducer of apoptosis, are increased according to the progression of this type of human arteriosclerosis, which is different from so-called atherosclerosis, Bax heterodimerizes with Bcl-2, an inhibitor of apoptosis, and the ratio of Bax to Bcl-2 determines cellular apoptosis or survival. Thus, we investigated apoptosis and the expressions of Bax, bax mRNA, and Bcl-2 in human arteriovenous (AV fistulas used for hemodialysis, a representative of arteriosclerosis of the aforementioned type. The material was 20 radial arteries obtained from 20 patients with chronic renal failure undergoing AV shunt surgery. SMCs, macrophages, and T lymphocytes were immunohistochemically identified at the light microscopic (LM) level. Apoptosis was detected by in situ terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-dUTP nick end labeling (TUNEL) at both the LM and electron microscopic (EM) level. Cell proliferating activity was estimated by proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were detected by immunohistochemistry and Western blot analysis. Expression of bax mRNA was detected by in situ hybridization, LM TUNEL-positive cells in both the intima and media were significantly increased according to the percent stenosis of the vessels. EM analysis revealed that ultrastructures of apoptotic SMCs were seen in both synthetic and contractile phenotypes. Their frequency of occurrence in the intima and media were greater in those vessels with >50% stenosis than in those with