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同型半胱氨酸与基质金属蛋白酶-3、-9 在升主动脉瘤患者中的表达。

Homocysteine and metalloprotease-3 and -9 in patients with ascending aorta aneurysms.

机构信息

Laboratory of Clinical Virology, Medical School, University of Crete, Voutes, 71409 Heraklion, Crete, Greece.

出版信息

Thromb Res. 2011 Nov;128(5):e95-9. doi: 10.1016/j.thromres.2011.07.008. Epub 2011 Jul 29.

Abstract

INTRODUCTION

Matrix metalloprotease (MMP) activity is increased in ascending and abdominal aortic aneurysms. Elevated plasma homocysteine (Hc) levels have been reported in patients with abdominal aneurysms. However, there are no published reports correlating, Hc and MMP levels in patients with ascending aortic aneurysms (AAAs).

MATERIALS AND METHODS

This study attempts to determine whether serum or tissue Hc in patients undergoing surgery for AAAs is associated with aneurysm diameter, circulating and tissue levels of MMP-3 and MMP-9 assessed by Enzyme-linked immunosorbent assay (ELISA) and their mRNA tissue expression assessed by real-time PCR. Twenty-seven patients were recruited in the study.

RESULTS

Forty-three percent of the patients had abnormal Hc serum levels (>35.9 μmol/L). Circulating MMP-3 (6.44±4.20 ng/mL) and MMP-9 levels (134±11.4 ng/mL) were elevated compared to healthy controls (p<0.001). Positive correlations were observed between circulating MMP-9, tissue MMP-3 and MMP-9 concentrations with serum Hc (r=0.773, p=0.011; r=0.461, p=0.014; r=0.526, p=0.024, respectively). MMP-9 mRNA was expressed in 21% of the aneurysms. No MMP-3 mRNA expression was detected in the studied specimens. A negative correlation between tissue Hc and aneurysm diameter was detected. No associations of serum Hc, MMP-3 and MMP-9 levels in both serum and tissue with aneurysm diameter were noted.

CONCLUSION

Our results suggest that Hc, even in patients with mild hyperhomocysteinaemia, is involved in the pathophysiology of AAA, through the regulation of MMP-3 and MMP-9 activity.

摘要

简介

基质金属蛋白酶(MMP)的活性在升主动脉和腹主动脉瘤中增加。已有报道称,腹主动脉瘤患者的血浆同型半胱氨酸(Hc)水平升高。然而,目前尚无关于升主动脉瘤(AAA)患者 Hc 和 MMP 水平相关性的报道。

材料和方法

本研究试图确定接受 AAA 手术的患者的血清或组织 Hc 是否与动脉瘤直径、通过酶联免疫吸附试验(ELISA)评估的循环和组织 MMP-3 和 MMP-9 水平以及通过实时 PCR 评估的组织表达相关。研究共招募了 27 名患者。

结果

43%的患者血清 Hc 水平异常(>35.9 μmol/L)。与健康对照组相比,循环 MMP-3(6.44±4.20 ng/mL)和 MMP-9 水平(134±11.4 ng/mL)升高(p<0.001)。循环 MMP-9、组织 MMP-3 和 MMP-9 浓度与血清 Hc 之间存在正相关(r=0.773,p=0.011;r=0.461,p=0.014;r=0.526,p=0.024)。在 21%的动脉瘤中检测到 MMP-9 mRNA 表达。在研究标本中未检测到 MMP-3 mRNA 表达。组织 Hc 与动脉瘤直径之间存在负相关。未观察到血清 Hc、MMP-3 和 MMP-9 水平与动脉瘤直径之间的相关性。

结论

我们的结果表明,Hc 甚至在轻度高同型半胱氨酸血症患者中,通过调节 MMP-3 和 MMP-9 的活性,参与 AAA 的病理生理学过程。

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