A novel role for relaxin-2 in the pathogenesis of primary varicosis.
BACKGROUND: Varicose veins affect up to 40% of men and up to 51% of women. The pathophysiology of primary varicosis is poorly understood. Theories ranging from incompetence of the venous valves to structural changes in the vein wall have been proposed. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the...
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doaj-5c89fda3104e458ea3b04819201d58e52020-11-25T01:48:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3902110.1371/journal.pone.0039021A novel role for relaxin-2 in the pathogenesis of primary varicosis.Julia AdamsSarah SchottArno BernMatthias RenzKristian IkenbergClaus GarbeChristian BuschBACKGROUND: Varicose veins affect up to 40% of men and up to 51% of women. The pathophysiology of primary varicosis is poorly understood. Theories ranging from incompetence of the venous valves to structural changes in the vein wall have been proposed. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the functional state of the intramural smooth muscle cells (n = 14 pairs matched for age and gender) and the expression of relaxin-2 and its receptors RXFP1 and RXFP2 in samples of varicose and healthy great saphenous veins (GSV) (n = 21 healthy GSV; n = 46 varicose GSV). Relaxin-2 and RXFP1 contents were determined in tissue samples (n = 9 samples per group). Pharmacological analyses were performed in a perfusion chamber. Morphometric determination of the nuclear size of the smooth muscle compartment yielded no significant difference in varicose GSV in comparison with the healthy controls. Relaxin-2 and its receptors were expressed in the muscular layer, endothelial cells and in blood vessels contained in the vein wall. Immunohistochemical expression of relaxin-2, RXFP1 and RXFP2 was significantly decreased in varicose GSV. Relaxin-2 and RXFP1 measured by ELISA and Western Blot were decreased in varicose GSV (relaxin-2 ELISA healthy vs. varicose GSV: 12.49±0.66 pg/mg versus 9.12±3.39 pg/mg of total protein; p = 0.01; Student's T-test). Contractions of vein samples induced by cholinergic or adrenergic stimulation were antagonized by relaxin-2. CONCLUSIONS/SIGNIFICANCE: We report that relaxin-2 and its receptors RXFP1 and RXFP2 are expressed in GSV and that their expression is significantly decreased in varicose GSV. Further, we were able to demonstrate a functional pharmacological relaxin-2 system in varicose GSV. Our results suggest a novel role for relaxin-2 in the pathogenesis of primary varicosis, rendering relaxin-2 a novel possible pharmacological agent for the treatment of this widely prevailing venous disease.http://europepmc.org/articles/PMC3380868?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia Adams Sarah Schott Arno Bern Matthias Renz Kristian Ikenberg Claus Garbe Christian Busch |
spellingShingle |
Julia Adams Sarah Schott Arno Bern Matthias Renz Kristian Ikenberg Claus Garbe Christian Busch A novel role for relaxin-2 in the pathogenesis of primary varicosis. PLoS ONE |
author_facet |
Julia Adams Sarah Schott Arno Bern Matthias Renz Kristian Ikenberg Claus Garbe Christian Busch |
author_sort |
Julia Adams |
title |
A novel role for relaxin-2 in the pathogenesis of primary varicosis. |
title_short |
A novel role for relaxin-2 in the pathogenesis of primary varicosis. |
title_full |
A novel role for relaxin-2 in the pathogenesis of primary varicosis. |
title_fullStr |
A novel role for relaxin-2 in the pathogenesis of primary varicosis. |
title_full_unstemmed |
A novel role for relaxin-2 in the pathogenesis of primary varicosis. |
title_sort |
novel role for relaxin-2 in the pathogenesis of primary varicosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
BACKGROUND: Varicose veins affect up to 40% of men and up to 51% of women. The pathophysiology of primary varicosis is poorly understood. Theories ranging from incompetence of the venous valves to structural changes in the vein wall have been proposed. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the functional state of the intramural smooth muscle cells (n = 14 pairs matched for age and gender) and the expression of relaxin-2 and its receptors RXFP1 and RXFP2 in samples of varicose and healthy great saphenous veins (GSV) (n = 21 healthy GSV; n = 46 varicose GSV). Relaxin-2 and RXFP1 contents were determined in tissue samples (n = 9 samples per group). Pharmacological analyses were performed in a perfusion chamber. Morphometric determination of the nuclear size of the smooth muscle compartment yielded no significant difference in varicose GSV in comparison with the healthy controls. Relaxin-2 and its receptors were expressed in the muscular layer, endothelial cells and in blood vessels contained in the vein wall. Immunohistochemical expression of relaxin-2, RXFP1 and RXFP2 was significantly decreased in varicose GSV. Relaxin-2 and RXFP1 measured by ELISA and Western Blot were decreased in varicose GSV (relaxin-2 ELISA healthy vs. varicose GSV: 12.49±0.66 pg/mg versus 9.12±3.39 pg/mg of total protein; p = 0.01; Student's T-test). Contractions of vein samples induced by cholinergic or adrenergic stimulation were antagonized by relaxin-2. CONCLUSIONS/SIGNIFICANCE: We report that relaxin-2 and its receptors RXFP1 and RXFP2 are expressed in GSV and that their expression is significantly decreased in varicose GSV. Further, we were able to demonstrate a functional pharmacological relaxin-2 system in varicose GSV. Our results suggest a novel role for relaxin-2 in the pathogenesis of primary varicosis, rendering relaxin-2 a novel possible pharmacological agent for the treatment of this widely prevailing venous disease. |
url |
http://europepmc.org/articles/PMC3380868?pdf=render |
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