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Chronic Venous Insufficiency: Transforming Growth Factor-β Isoforms and Soluble Endoglin Concentration in Different States of Wound Healing

1
Department of Biomolecular Sciences, Section of Clinical Biochemistry and Molecular Genetics, University “Carlo Bo”, 61029 Urbino, Italy
2
Department of Angiology, Barbantini Clinic, via del Calcio 2, 55100 Lucca, Italy
3
Vascular Surgery Division, VA Boston Healthcare System, West Roxbury, Boston, MA 02130, USA
4
Harvard Medical School, Brigham and Women’s Hospital, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(10), 2206; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18102206
Received: 5 September 2017 / Revised: 18 October 2017 / Accepted: 19 October 2017 / Published: 21 October 2017
(This article belongs to the Special Issue Molecular Research on Chronic Venous Disease)
Venous leg ulcer (VLU) is a huge healthcare problem with poorly understood pathophysiology. Transforming growth factor-β (TGF-β) and endoglin (Eng), are inflammatory and wound healing mediators. Eng, co-receptor for TGF-β type-II receptors, may be cleaved forming soluble Eng (sEng), antagonizing TGF-β signaling, a crucial process in vascular pathologies. We evaluated the accumulation in wound fluid (WF) of TGF-β isoforms and sEng in healing stages, showing the effects of sulodexide treatments, a glycosaminoglycan with clinical efficacy in VLU healing. Patients with inflammatory (Infl) and granulating (Gran) VLU were recruited. WFs and THP-1 monocytes exposed to Infl and Gran WF (treated/untreated with sulodexide) were analyzed for TGF-β isoforms and sEng by multiplex immunoassay. In both Infl and Gran WF, TGF-β1 and β2 were similar; TGF-β3 was significantly increased in Infl compared to Gran WFs (p = 0.033). sEng was significantly elevated in Gran compared to Infl WFs (p = 0.002). In THP-1 monocytes there was a significant increase in sEng after co-treatment of WF and sulodexide. The increase in TGF-β3 found in Infl WF highlights its negative effect on wound healing, while the increased levels of sEng in Gran WF affects the leukocyte adhesion/transmigration through the endothelium, reducing the inflammatory response and favoring the wound healing. Glycosaminoglycan sulodexide potentiates the effects of sEng release from monocyte, representing an important therapeutic option for wound healing. View Full-Text
Keywords: chronic venous insufficiency; inflammation; glycosaminoglycan; sulodexide; venous leg ulcer; wound healing; soluble endoglin; transforming growth factor beta isoforms; monocyte chronic venous insufficiency; inflammation; glycosaminoglycan; sulodexide; venous leg ulcer; wound healing; soluble endoglin; transforming growth factor beta isoforms; monocyte
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MDPI and ACS Style

Ligi, D.; Croce, L.; Mosti, G.; Raffetto, J.D.; Mannello, F. Chronic Venous Insufficiency: Transforming Growth Factor-β Isoforms and Soluble Endoglin Concentration in Different States of Wound Healing. Int. J. Mol. Sci. 2017, 18, 2206. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18102206

AMA Style

Ligi D, Croce L, Mosti G, Raffetto JD, Mannello F. Chronic Venous Insufficiency: Transforming Growth Factor-β Isoforms and Soluble Endoglin Concentration in Different States of Wound Healing. International Journal of Molecular Sciences. 2017; 18(10):2206. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18102206

Chicago/Turabian Style

Ligi, Daniela, Lidia Croce, Giovanni Mosti, Joseph D. Raffetto, and Ferdinando Mannello. 2017. "Chronic Venous Insufficiency: Transforming Growth Factor-β Isoforms and Soluble Endoglin Concentration in Different States of Wound Healing" International Journal of Molecular Sciences 18, no. 10: 2206. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18102206

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