BackgroundVaricose 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 FindingsWe 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/SignificanceWe 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.
With the novel microperfusion system, isotonic contractions of smooth muscle in the USL can be recorded and quantified in the tissue microenvironment on the microscopic level. The USL smooth muscle is cholinergic, stimulated by oxytocin and modulated by relaxin.
In the USL the smooth muscle extends into the adventitial layer of blood vessels and forms a functional unit with the vascular plexus, which is regulated by relaxin and oxytocin.
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