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从性别角度看腹主动脉瘤的生物标志物。

Biomarkers for abdominal aortic aneurysms from a sex perspective.

作者信息

Villard Christina, Wågsäter Dick, Swedenborg Jesper, Eriksson Per, Hultgren Rebecka

机构信息

Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Gend Med. 2012 Aug;9(4):259-266.e2. doi: 10.1016/j.genm.2012.05.002. Epub 2012 Jun 20.

DOI:10.1016/j.genm.2012.05.002
PMID:22721599
Abstract

BACKGROUND

Abdominal aortic aneurysms (AAAs) differ in men and women. Women are older at diagnosis, have a higher risk of rupture, and worse outcome after surgery compared with men. The higher occurrence of AAAs in men accounts for the dominance of men in biomarker analyses.

OBJECTIVE

The primary aim of this study was to investigate levels of established biomarkers for AAA in men and women, and the secondary aim was to compare biomarker levels in women with and without AAAs.

METHODS

In this prospective case-control study, blood samples were collected from 16 women and 18 men with AAAs ≥5.5 cm, from 20 women with AAAs <5.5 cm, and from 18 women with peripheral artery disease (PAD). Plasma concentrations of matrix metalloproteinase (MMP) -2, -9, and -13; tissue inhibitor of MMP-1 (TIMP-1); plasminogen activator inhibitor 1 (PAI-1); high-sensitivity C-reactive protein (hsCRP); and estradiol levels were analyzed by ELISA. An ultrasound examination was performed in women with PAD to exclude an AAA.

RESULTS

Age and other comorbid conditions were similar between men and women with AAAs. Women with AAAs had higher levels of MMP-9 compared with men with equally large AAAs (42.8 ng/mL vs 36.2 ng/mL, P = 0.036) and lower levels of estradiol (30.0 pmoL vs 86.5 pmol/L, P < 0.001). Women with AAAs had lower levels of MMP-9 compared with women without (59.5 ng/mL vs 132.6 ng/mL, P = 0.010). There was no significant difference in the plasma levels of MMP-2, MMP-13, hsCRP, PAI-1, TIMP-1, and estradiol between women with and without AAAs.

CONCLUSION

The higher levels of MMP-9 in women compared with men with equally large AAAs could suggest that MMP-9 is a biomarker related to the sex differences in aneurysm development. The lower levels of estradiol in women with AAAs compared with men suggest that the possible protective effect of endogenous estrogen cannot be explained by a difference in circulating levels of estradiol.

摘要

背景

腹主动脉瘤(AAA)在男性和女性中存在差异。女性在诊断时年龄较大,破裂风险较高,与男性相比,手术后的预后较差。男性AAA发病率较高导致男性在生物标志物分析中占主导地位。

目的

本研究的主要目的是调查男性和女性中已确定的AAA生物标志物水平,次要目的是比较有和没有AAA的女性的生物标志物水平。

方法

在这项前瞻性病例对照研究中,从16名患有≥5.5 cm AAA的女性、18名患有≥5.5 cm AAA的男性、20名患有<5.5 cm AAA的女性以及18名患有外周动脉疾病(PAD)的女性中采集血样。通过酶联免疫吸附测定法(ELISA)分析血浆中基质金属蛋白酶(MMP)-2、-9和-13、MMP-1组织抑制剂(TIMP-1)、纤溶酶原激活物抑制剂1(PAI-1)、高敏C反应蛋白(hsCRP)和雌二醇水平。对患有PAD的女性进行超声检查以排除AAA。

结果

患有AAA的男性和女性在年龄和其他合并症方面相似。与患有同样大小AAA的男性相比,患有AAA的女性MMP-9水平更高(42.8 ng/mL对36.2 ng/mL,P = 0.036),雌二醇水平更低(30.0 pmoL对86.5 pmol/L,P < 0.001)。与没有AAA的女性相比,患有AAA的女性MMP-9水平更低(59.5 ng/mL对132.6 ng/mL,P = 0.010)。有和没有AAA的女性之间,血浆中MMP-2、MMP-13、hsCRP、PAI-1、TIMP-1和雌二醇水平没有显著差异。

结论

与患有同样大小AAA的男性相比,女性MMP-9水平更高,这可能表明MMP-9是一种与动脉瘤发展中的性别差异相关的生物标志物。与男性相比,患有AAA的女性雌二醇水平更低,这表明内源性雌激素的可能保护作用不能用循环雌二醇水平的差异来解释。

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