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血管内皮生长因子在多发性肌炎患者和皮肌炎患者的肌肉组织中高表达。

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis.

作者信息

Grundtman Cecilia, Tham Emma, Ulfgren Ann-Kristin, Lundberg Ingrid E

机构信息

Rheumatology Research Unit, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.

出版信息

Arthritis Rheum. 2008 Oct;58(10):3224-38. doi: 10.1002/art.23884.

Abstract

OBJECTIVE

To investigate the expression of vascular endothelial growth factor (VEGF) in muscle biopsy specimens and serum from patients with polymyositis and patients with dermatomyositis compared with that in healthy control subjects.

METHODS

Muscle biopsy specimens from 33 patients with polymyositis or dermatomyositis and 15 healthy control subjects and serum samples from 56 patients and 56 healthy control subjects were analyzed. Patients were categorized into 3 groups, depending on disease duration and the presence or absence of inflammatory infiltrates. The expression of VEGF and the vessel marker CD31 in muscle was analyzed by immunohistochemistry, the expression of VEGF messenger RNA (mRNA) was analyzed by in situ hybridization, and serum levels of VEGF were determined by enzyme-linked immunosorbent assay.

RESULTS

Patients with polymyositis or dermatomyositis in the early or chronic phase without inflammatory infiltrates had a decreased total number of capillaries compared with healthy individuals. In patients with early disease without inflammatory infiltrates, the number of VEGF-expressing muscle fibers was increased compared with that in control subjects, whereas VEGF expression was unchanged in the chronic phase of disease. In patients with established disease with inflammatory infiltrates, total VEGF expression was high compared with that in healthy control subjects. In healthy control subjects, VEGF was expressed in endothelial cells and in occasional muscle fibers. VEGF mRNA was expressed in muscle fibers in both healthy individuals and patients. The level of serum VEGF was significantly increased in patients compared with control subjects.

CONCLUSION

Our observations support a role of VEGF in the early phases of polymyositis and dermatomyositis. A reduced number of capillaries could lead to induction of VEGF expression in muscle fibers. Furthermore, differences in molecular expression during certain phases of disease may help in the development of specific therapeutic algorithms in the treatment of myositis.

摘要

目的

研究与健康对照者相比,多发性肌炎患者和皮肌炎患者肌肉活检标本及血清中血管内皮生长因子(VEGF)的表达情况。

方法

分析了33例多发性肌炎或皮肌炎患者及15例健康对照者的肌肉活检标本,以及56例患者和56例健康对照者的血清样本。根据疾病持续时间和炎症浸润的有无,将患者分为3组。采用免疫组织化学法分析肌肉中VEGF和血管标志物CD31的表达,采用原位杂交法分析VEGF信使核糖核酸(mRNA)的表达,采用酶联免疫吸附测定法测定血清VEGF水平。

结果

与健康个体相比,处于早期或慢性期且无炎症浸润的多发性肌炎或皮肌炎患者的毛细血管总数减少。在无炎症浸润的早期疾病患者中,与对照者相比,表达VEGF的肌纤维数量增加,而在疾病慢性期VEGF表达无变化。在有炎症浸润的确诊疾病患者中,与健康对照者相比,VEGF总表达量较高。在健康对照者中,VEGF在内皮细胞和偶尔的肌纤维中表达。VEGF mRNA在健康个体和患者的肌纤维中均有表达。与对照者相比,患者血清VEGF水平显著升高。

结论

我们的观察结果支持VEGF在多发性肌炎和皮肌炎早期阶段发挥作用。毛细血管数量减少可能导致肌纤维中VEGF表达的诱导。此外,疾病某些阶段分子表达的差异可能有助于制定治疗肌炎的特定治疗方案。

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