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热休克蛋白27在人类动脉粥样硬化斑块中的表达及急性冠状动脉综合征患者血浆热休克蛋白27水平升高

Expression of heat shock protein 27 in human atherosclerotic plaques and increased plasma level of heat shock protein 27 in patients with acute coronary syndrome.

作者信息

Park Haing Kee, Park Eui-Chul, Bae Sung Won, Park Mi Young, Kim Seon Woon, Yoo Hwan Soo, Tudev Munkhtsetseg, Ko Young Hye, Choi Yoon-Ho, Kim Sungjoo, Kim Dong-Ik, Kim Young Wook, Lee Byung Boong, Yoon Jong-Bok, Park Jeong Euy

机构信息

Division of Cardiology, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea.

出版信息

Circulation. 2006 Aug 29;114(9):886-93. doi: 10.1161/CIRCULATIONAHA.105.541219. Epub 2006 Aug 21.

Abstract

BACKGROUND

We intended to identify proteins that are differentially expressed in human atherosclerotic plaques.

METHODS AND RESULTS

Comparative 2-dimensional electrophoretic analysis on carotid atherosclerotic endarterectomy specimens (n = 10) revealed that heat shock protein 27 (Hsp27) expression was significantly increased in the nearby normal-appearing area compared with the plaque core area from the same vessel specimen, which was further confirmed by Western blot analysis. The Hsp27 expression in the adjacent normal-appearing vessel areas was much higher than that in nonatherosclerotic reference arteries. The phosphorylation of Hsp27 showed a gradation in the degree of phosphorylation: greatest in the reference arteries, intermediate in the adjacent normal-appearing area, and lowest in plaque core area. Immunohistochemical analysis showed that the phosphorylation of Hsp27 of smooth muscle cells in the carotid endarterectomy specimens was decreased compared with that in the reference artery specimen. The mean plasma level of Hsp27 was significantly higher in patients with acute coronary syndrome (ACS) (n = 27; 106.1 +/- 74.1 ng/mL) than in the normal reference subjects (n = 29; 45.8 +/- 29.5 ng/mL; P < 0.005). The plasma levels of Hsp27 were significantly correlated with those of heat shock protein 70 (Hsp70) (r = 0.422, P < 0.0005), with adjustment for ACS/reference status.

CONCLUSIONS

In the atherosclerotic lesion, Hsp27 expression is increased in the normal-appearing vessel adjacent to atherosclerotic plaque, whereas levels in the plaque itself are significantly decreased. Both plaque and adjacent artery show decreased Hsp27 phosphorylation compared with reference vessel. In ACS, plasma Hsp27 and Hsp70 are increased, and levels of Hsp27 correlate with Hsp70, C-reactive protein, and CD40L levels.

摘要

背景

我们旨在鉴定在人类动脉粥样硬化斑块中差异表达的蛋白质。

方法与结果

对颈动脉粥样硬化内膜切除术标本(n = 10)进行二维电泳比较分析,结果显示,与同一血管标本的斑块核心区域相比,在外观正常的临近区域热休克蛋白27(Hsp27)表达显著增加,这一结果通过蛋白质印迹分析得到进一步证实。在临近的外观正常的血管区域中Hsp27的表达远高于非动脉粥样硬化对照动脉。Hsp27的磷酸化呈现出磷酸化程度的梯度变化:在对照动脉中最高,在临近的外观正常区域居中,在斑块核心区域最低。免疫组织化学分析显示,与对照动脉标本相比,颈动脉内膜切除术标本中平滑肌细胞的Hsp27磷酸化减少。急性冠状动脉综合征(ACS)患者(n = 27;106.1±74.1 ng/mL)的Hsp27平均血浆水平显著高于正常对照受试者(n = 29;45.8±29.5 ng/mL;P < 0.005)。校正ACS/对照状态后,Hsp27的血浆水平与热休克蛋白70(Hsp70)的血浆水平显著相关(r = 0.422,P < 0.0005)。

结论

在动脉粥样硬化病变中,与动脉粥样硬化斑块相邻的外观正常的血管中Hsp27表达增加,而斑块本身的水平显著降低。与对照血管相比,斑块和临近动脉均显示Hsp27磷酸化减少。在ACS中,血浆Hsp27和Hsp70升高,且Hsp27水平与Hsp70、C反应蛋白及CD40L水平相关。

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