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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Volume 53, Issue 9

Issues

Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas

Porfyrios Korompelis / Christina Piperi / Christos Adamopoulos / Georgia Dalagiorgou / Penelope Korkolopoulou / Athanasia Sepsa / Aris Antsaklis
  • Department of Obstetrics and Gynaecology, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Athanasios G. Papavassiliou
Published Online: 2014-12-03 | DOI: https://doi.org/10.1515/cclm-2014-0798

Abstract

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 immunohistochemistry 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 patients compared 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.

Keywords: matrix metalloproteinase (MMP)-2; MMP-9; TIMP-1; uterine leiomyomas; vascular endothelial growth factor (VEGF)-A

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About the article

Corresponding author: Christina Piperi, Department of Biological Chemistry, University of Athens Medical School, 75 M. Asias Street, 11527 Athens, Greece, Phone: +30 210 7462610, Fax: +30 210 7791207, E-mail:

aChristina Piperi and Christos Adamopoulos contributed equally to this work.


Received: 2014-08-05

Accepted: 2014-10-27

Published Online: 2014-12-03

Published in Print: 2015-08-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 53, Issue 9, Pages 1415–1424, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2014-0798.

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