title: Chronic venous disease - Part I: Inflammatory biomarkers in wound healing.
abstract: Venous leg ulcers (VLUs) produce wound fluid (WF), as a result of inflammatory processes within the wound. It is unclear if WF from different healing phases of VLU has a peculiar biochemical profile and how VLU microenvironment affects the wound healing mechanisms. This study was conducted to evaluate the cytokine/chemokine profiles in WF from distinct VLU phases, in WF- and LPS-stimulated monocytes and treated with glycosaminoglycan Sulodexide, a therapeutic option for VLU healing. WF and plasma were collected from patients with VLU during active inflammatory (Infl) and granulating (Gran) phases. Demographics, clinical characteristics and pain measurements were evaluated. WF, plasma, and THP-1 supernatants were analyzed for 27 inflammatory mediators by multiplex immunoassay. Our results demonstrated that: 1) pain was significantly increased in patients with Infl compared to Gran VLU; 2) cytokine profile of Infl WF was found to be statistically different from that Gran WF, as well significantly increased respect to plasma; 3) LPS- and WF-stimulation of THP-1 cells significantly increased the expression of several cytokines compared to untreated cells; 4) Sulodexide treatment of both LPS- and WF-stimulated THP-1 monocytes was able to significantly down-regulate the release of peculiar inflammatory mediators. Our study highlighted the importance to understand biomolecular processes underlying CVI when providing treatment for chronic VLU. Identification of inflammatory biomarkers in leg ulcer microenvironment, may provide useful tools for predicting healing outcome and developing targeted therapies.
authors.affiliation: Department of Biomolecular Sciences, Section of Clinical Biochemistry and Molecular Genetics, University "Carlo Bo", Urbino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ligi
authors.affiliation: Department of Angiology, Barbantini Clinic, via del Calcio 2, 55100 Lucca, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mosti
authors.affiliation: Department of Biomolecular Sciences, Section of Clinical Biochemistry and Molecular Genetics, University "Carlo Bo", Urbino, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Croce
authors.affiliation: Vascular Surgery Division, VA Boston Healthcare System, West Roxbury, MA, USA; Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Raffetto
authors.affiliation: Department of Biomolecular Sciences, Section of Clinical Biochemistry and Molecular Genetics, University "Carlo Bo", Urbino, Italy. Electronic address: ferdinando.mannello@uniurb.it.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Mannello
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D060833:Cellular Microenvironment; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D000074084:THP-1 Cells; D014647:Varicose Ulcer / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers
keywords: Chronic venous insufficiency; Glycosaminoglycan; Inflammation; Sulodexide; Venous leg ulcer; Wound healing