Peptide growth factors and their receptors in the vein wall.

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-ß1, 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-ß1, VEGF, IGF-1R, VEGF R1 and VEGF R2 were assessed with ELISA method. Protein expression of FGF R1 and TGF-ß 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-ß 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-ß 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.

Divergent changes in the content and activity of MMP-26 and TIMP-4 in human umbilical cord tissues associated with preeclampsia.

OBJECTIVES: Preeclampsia is the most common disorder associated with pregnancy. Our earlier findings revealed a substantial increase in the amount of matrix metalloproteinase-26 (matrilysin 2; MMP-26) in preeclamptic umbilical cord blood. The role of MMP-26 in preeclamptic umbilical cord tissue has not been fully elucidated. Some reports have indicated that the expression of matrilysin 2 and tissue inhibitor of matrix metalloproteinase 4 (TIMP-4) is coordinately regulated during progression of various diseases. STUDY DESIGN: Therefore, we decided to assess the expression and activity of MMP-26 and TIMP-4 in normal and preeclamptic umbilical cord tissues - umbilical cord arteries (UCA), vein (UCV) and Wharton's jelly (WJ). Tissues obtained from 10 normal (control material) and 10 preeclamptic umbilical cords were assessed using immunoenzymatic assay, Western immunoblotting, reverse transcriptase - polymerase chain reaction and fluorometric determination of the enzyme activity. RESULTS: All umbilical cord tissues, both control and preeclamptic, expressed MMP-26 and TIMP-4 in macromolecular complexes. Preeclampsia induced a significant increase in the content and actual activity of MMP-26 in UCV and WJ, as compared to control. The content of TIMP-4 in preeclamptic UCV and WJ was reduced. The content of MMP-26 mRNA was lower in UCA and UCV, whereas higher in WJ in preeclampsia. CONCLUSIONS: Divergent changes in MMP-26 mRNA and protein expression suggest a difference in the factors controlling the matrilysin synthesis in healthy and preeclamptic subjects. The decrease in TIMP-4 content in preeclamptic UCV might be the main reason for significantly higher actual activity of MMP-26 in that tissue. Only in preeclamptic Wharton's jelly the changes were compatible in terms of the content and activity of MMP-26 and TIMP-4. It cannot be excluded that similar alterations can be observed for the whole vascular system of newborns delivered by mothers with preeclampsia.