title: Venous ulcer: what is new?
abstract: The pathophysiology of venous dermal abnormality in chronic venous ulcers is reflective of a complex interplay that involves sustained venous hypertension, inflammation, changes in the microcirculation, cytokine and matrix metalloproteinase activation, and altered cellular function. Red blood cells and macromolecules extravasate into the interstitium and activate endothelial cells. Endothelial expression of specific adhesion molecules recruits leukocytes and causes diapedesis of these cells into the dermal microvasculature, promoting an inflammatory response with activation of cytokines and proteinases. Altered cell function enhances a state of vulnerability in the surrounding tissues, initiating specific changes associated with venous disease. Ultimately, the persistent inflammatory-proteinase activity leads to advanced chronic venous insufficiency and ulcer formation. The mainstay of therapy in venous ulcer abnormality is correction of the underlying venous hypertension through compression therapy and/or surgery. Understanding the science involved in the pathophysiology of venous ulcer formation has led to the development of adjunctive treatment directed at the dysregulated molecular pathways. Randomized clinical trials are critical for determining the most effective evidence-based treatments for venous ulcer, and this review discusses important trials that have had a significant impact on venous ulcer healing. In addition, the authors have included subsections referred to as "Translational Implications for Therapy" in the basic science sections of the review to help bridge the basic science knowledge with clinical applications that may help to modulate the molecular abnormalities in the pathophysiologic cascade leading to venous ulcers.
authors.affiliation: Boston and West Roxbury, Mass.; and Chapel Hill, N.C. From Harvard Medical School, Brigham and Women's Hospital; Veterans Affairs Boston Healthcare System; and the University of North Carolina School of Medicine.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Raffetto
authors.forename: William A
authors.initials: WA
authors.lastname: Marston
mesh_terms: D002908:Chronic Disease; D006801:Humans; D014647:Varicose Ulcer / Q000276:immunology / Q000503:physiopathology / Q000628:therapy