The varicose vein wall remodeling is a very complex process, which is controlled by numerous factors, including peptide growth factors. The aim of the study was to assess a/b FGF, IGF-1, TGF-β1, VEGF-A and their receptors in the vein wall. Varicose vein samples were taken from 24 patients undergoing varicose vein surgery. The control material consisted of vein specimens collected from 12 patients with chronic limb ischemia. Contents of aFGF, bFGF, IGF-I, TGF-β1, VEGF, IGF-1R, VEGF R1 and VEGF R2 were assessed with ELISA method. Protein expression of FGF R1 and TGF-β RII were evaluated with western blot. Increased contents of aFGF, IGF-1 and VEGF-A were found in varicose veins in comparison with normal ones (p<0.05). In contrast, a significant decrease in TGF-β content was demonstrated in varicose veins (p<0.05). Furthermore, there was no difference in bFGF content in both groups (p>0.05). IGF-1 R content was significantly increased in varicose veins (p<0.05). There was no difference in VEGF R1 content between varicose and normal veins (p>0.05), whereas VEGF R2 content was significantly increased in varicose veins (p<0.05). Western blot demonstrated increased expression of TGF-β RII in varicose veins (p<0.05) and similar expression of FGF R1 in both groups (p>0.05). Demonstrated changes in peptide growth factors and their receptors may disturb metabolism of extracellular matrix in the varicose vein wall and contribute to the development of the disease to its more advanced stages.
Purpose: Multiple cellular functions are stimulated by a Insulin-like Growth Factor-I (IGF-I). The biological activity of IGF-I is modulated by IGFbinding proteins (IGF-BPs) and at the same time, the availability of IGF-BPs may be regulated by the proteolytic activity of some metalloproteinases (MMPs). The aim of the present study was to compare the amounts of IGF-I and IGF-BPs in relation to the activity of MMP-9 in serum and knee synovial fluid from patients with Lyme arthritis (LA) and post-traumatic damage (PTD). Material and methods: Serum and synovial fluids were taken from knee joints of patients with PTD and LA. ELISA (for IGF-I assay), polyacrylamine gel electrophoresis following Western immuneblotting (for IGF-I and IGF-BPs expression), and zymography (for metalloproteinases detection), were used. Results: The concentration of IGF-I in serum and synovial fluid from LA patients were significantly lowered in comparison to PTD patients. Interesting, the synovial fluid /serum ratio of IGF-I concentrations was also lower in LA patients. Low expression IGF-BP3 and high activity of MMP-9 were detected in the LA synovial fluid. Conclusions: The high proteolytic activity of MMP- 9 results in a cleavage of both IGF-I and IGF-BP3 causing a decrease in content of these substances in LA synovial fluid. In addition, the reduction in IGF and IGF-BP amounts may affect the repair processes in joint tissues of LA patients. The low concentration of IGF-I and IGF-BP3 slows down the repair processes in the joint tissues of LA patients.
The progressive damage of human articular cartilage is associated with loss of integrity of its extracellular matrix components. Their metabolism is under the control of cytokines produced locally. It is known that peptide growth factors stimulate chondrocytes to synthesize matrix components, and other cytokines, such as interleukins, promote their catabolism by stimulation of chondrocytes to the production of enzymes degrading components of cartilage. The aim of this study was evaluation the presence of inulin-like growth factors (IGFs) in synovial fluid and blood serum of patients with rheumatoid arthritis and osteoarthritis and their binding proteins and matrix metalloproteinases that regulate their bioavailability using Western Immunoblot, ELISA test and zymography technique. The results showed that both IGFs were present, first of all, in the form of high molecular complexes with their specific binding proteins. In this way those proteins prolonged growth factors' half-life but suppressed their bioavailability for receptors and action on target cells. Low content of free IGF-I indicated limitation of its anabolic influence on cartilage metabolism of patients with both diseases.
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