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首页> 外文期刊>Clinical chemistry and laboratory medicine: CCLM >Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas
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Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas

机译：血管平滑肌瘤中血管内皮因子A，明胶酶（MMP-2，MMP-9）和TIMP-1的表达

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Background: Leiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas.Methods: Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immu-nohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography. Results: Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patientscompared to controls (p<0.001, p=0.004, p=0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p=0.021) as well as MMP-9 (p=0.001) peripheral levels in the patient's group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues. Conclusions: This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance.
机译：背景：平滑肌瘤的生长涉及细胞肥大，有丝分裂活性的调节和细胞外基质（ECM）的上调。血管因子和基质金属蛋白酶（MMP）在肿瘤形成和组织重塑中起协调作用。本研究探讨血管生成因子血管内皮生长因子（VEGF）-A与主要明胶酶，MMP-2 / MMP-9及其组织抑制剂TIMP-1的活性在平滑肌瘤中的作用。方法：46名外周血子宫平滑肌瘤的女性在子宫切除术之前获得，通过酶联免疫吸附试验与39个健康对照相比，评估VEGF-A，MMP-2，-9，TIMP-1的水平。子宫切除术后平滑肌瘤组织标本通过Western免疫印迹和免疫组织化学评估VEGF-A，MMP-2和MMP-9的蛋白表达水平。此外，通过半定量酶谱法评估平滑肌瘤组织提取物和对照肌层中明胶酶的活性。结果：与对照组相比，平滑肌瘤患者的VEGF-A，MMP-2和TIMP-1的循环水平显着升高（分别为p <0.001，p = 0.004，p = 0.003）。在患者组中，VEGF-A和MMP-2（p = 0.021）以及MMP-9（p = 0.001）周围水平之间发现正相关。此外，与对照肌层相比，在平滑肌瘤组织中检测到增加的VEGF-A蛋白水平，随后在平滑肌细胞的平滑肌细胞ECM包扎中VEGF-A和MMP-2的定位增加。在所有研究的组织中，平滑肌瘤中MMP-2的活性均显着高于正常子宫肌层。结论：本研究证明VEGF-A和MMP-2在子宫平滑肌瘤生长和血管生成中可能具有协同作用，具有潜在的预后意义。

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