ABSTRACT
OBJECTIVE: Venous ulcer fibroblasts (w-fb) have attenuated growth compared to normal fibroblasts (n-fb). The MAPKp38 pathway mediates stress-responses in various diseases. We hypothesize that p38 pathway is altered in w-fb. METHODS: W-fb were isolated from venous ulcers and n-fb from the ipsilateral thigh. Fibroblasts were analyzed for phosphorylated p38 using immunoblot. The relation between p38 and w-fb proliferation was assessed with SB203580 (p38 inhibitor). Fibroblasts were treated with bFGF, TNF-a, and IL-1 and p38 expression analyzed. RESULTS: Phosphorylated p38 expression was increased in w-fb (AU%=233.5+/-59.7, P=0.039) compared to n-fb (AU%=99.9+/-14.6). W-fb treated with SB203580 demonstrated increased growth compared to untreated w-fb. W-fb treated with bFGF demonstrated decreased p38. TNF-alpha and IL-1beta significantly increase p38 expression. CONCLUSIONS: MAPK p38 is up-regulated in w-fb. Regulation of w-fb proliferation is influenced by p38. Altering the p38 pathway in vivo with growth factors or cytokine inhibition may improve fibroblast proliferation and venous ulcer healing.
Subject(s)
Cell Proliferation , Fibroblasts/enzymology , Varicose Ulcer/enzymology , p38 Mitogen-Activated Protein Kinases/metabolism , Adult , Aged , Cell Proliferation/drug effects , Cells, Cultured , Female , Fibroblast Growth Factor 2/metabolism , Fibroblasts/drug effects , Fibroblasts/pathology , Humans , Imidazoles/pharmacology , Interleukin-1/metabolism , Male , Middle Aged , Phosphorylation , Protein Kinase Inhibitors/pharmacology , Pyridines/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation , Varicose Ulcer/pathology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitorsABSTRACT
The creation and long-term management of dialysis accesses has been and remains a challenging aspect of vascular surgery practice. Until recently, vascular surgeons relied on open techniques to salvage and maintain dialysis fistulas and grafts. In the last 10 years, percutaneous approaches have become widely adopted and to this day continue to be refined as new devices and techniques are developed. Recent series have found similar technical success rates to open surgery, with the best results seen in the treatment of short-segment and anastomotic stenoses. Percutaneous interventions also allow for treatment of remote and surgically inaccessible lesions such as central vein stenoses. Some of the pitfalls of this approach include the exposure to thrombolytics, intravenous contrast, and radiation. Nevertheless, despite these limitations, a percutaneous approach has become first-line therapy in dialysis access management.
