title: Pathophysiology of wound healing and alterations in venous leg ulcers-review.
abstract: Venous leg ulcer (VLU) is one of the most common lower extremity ulcerated wound, and is a significant healthcare problem with implications that affect social, economic, and the well-being of a patient. VLU can have debilitating related problems which require weekly medical care and may take months to years to heal. The pathophysiology of VLU is complex, and healing is delayed in many patients due to a persistent inflammatory condition. Patient genetic and environmental factors predispose individuals to chronic venous diseases including VLU. Changes in shear stress affecting the glycocalyx are likely initiating events, leading to activation of adhesion molecules on endothelial cells, and leukocyte activation with attachment and migration into vein wall, microcirculation, and in the interstitial space. Multiple chemokines, cytokines, growth factors, proteases and matrix metalloproteinases are produced. The pathology of VLU involves an imbalance of inflammation, inflammatory modulators, oxidative stress, and proteinase activity. Understanding the cellular and biochemical events that lead to the progression of VLU is critical. With further understanding of inflammatory pathways and potential mechanisms, certain biomarkers could be revealed and studied as both involvement in the pathophysiology of VLU but also as therapeutic targets for VLU healing.
authors.affiliation: Boston VA Health Care System, Vascular Surgery, Boston, MA, USA Brigham and Women's Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA joseph.raffetto@med.va.gov.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Raffetto
mesh_terms: D002465:Cell Movement; D002908:Chronic Disease; D017364:Collagenases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D019276:Glycocalyx / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D007871:Leg Ulcer / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing
chemical_list: D016207:Cytokines; D017364:Collagenases
keywords: Venous leg ulcer; chemokines; collagen; cytokines; endothelial cells; extracellular matrix; fibroblasts; free radical; glycocalyx; growth factors; inflammation; iron; leukocytes; macrophages; matrix metalloproteinases; oxidative stress; wound; wound healing