Microcirculation and venous ulcers: a review.
Recent histological and immunocytochemical analyses of venous leg ulcers suggest that lesions observed in the different stages of chronic venous insufficiency (CVI) may be related to an inflammatory process. This inflammatory process leads to fibrosclerotic remodeling of the skin and then to ulceration. The vascular network of the most superficial layers of the skin appears to be the target of the inflammatory reaction. Hemodynamic forces such as venous hypertension, circulatory stasis, and modified conditions of shear stress appear to play an important role in an inflammatory reaction accompanied by leukocyte activation which clinically leads to CVI: venous dermatitis and venous ulceration. The leukocyte activation is accompanied by the expression of integrins and by synthesis and release of many inflammatory molecules, including proteolytic enzymes, leukotrienes, prostaglandin, bradykinin, free oxygen radicals, cytokines, and possibly other classes of inflammatory mediators. The inflammatory reaction perpetuates itself, leading to liposclerotic skin and subcutaneous tissue remodeling. In light of the mechanisms of venous ulcer formation cited above, therapy in the future might be directed against leukocyte activation in order to diminish the magnitude of the inflammatory response. With this in mind, the attention of many investigators has been drawn to two different drugs with an anti-inflammatory effect: pentoxifylline and flavonoids.
Pascarella
Luigi
L
Department of Bioengineering, Whitaker Institute of Biomedical Engineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA.
Schönbein
Geert W Schmid
GW
Bergan
John J
JJ
D004730:Endothelium, Vascular / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood*; D039041:Integrin alpha4beta1 / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007962:Leukocytes / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000097:blood; D008833:Microcirculation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014647:Varicose Ulcer / Q000503:physiopathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D018836:Inflammation Mediators; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1