BACKGROUND: Cardiotrophin-1 (CT-1), a member of the IL-6 superfamily, is elevated in the serum of patients with ischemic and valvular heart disease. In this study, we hypothesized that CT-1 induces endothelial cell angiogenesis and that the ADMA/DDAH pathway plays an important role in the process. METHODS: pEGFP-N1-CTF1-GFP and pEGFP-N1 were constructed and used to transiently transfect to HUVECs, mediated by LipofectamineTM 2000. After transfection, the expression of CT-1 was examined by qRT-PCR and western blotting. Endothelial cell proliferation assay was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) method. Migration assay was performed using transwell, tube formation test was examined on Matrigel, eNOSmRNA expression was assayed by qRT-PCR, DDAH I, DDAHII and VEGF expression were detected by western blotting, the level of ADMA and the activity of DDAH were measured by High Performance Liquid Chromatography, NOS activity and the concentration of NO were assayed by L-[3H] citrulline production from L-[3H]arginine. RESULTS: Overexpression of CT-1, increased endothelial cell proliferation, migration and formation of blood vessels, upregulated the expression of eNOSmRNA, DDAHI, DDAHII and VEGF, elevated the activity of DDAH and NOS, decreased the level of ADMA and promoted NO synthesis. In contrast, ADMA partially inhibited the effects of CT-1 induction. CONCLUSIONS: Overexpression of CT-1 increases cell proliferation, migration and formation of blood vessels. This result also suggests that CT-1 may regulate angiogenesis through the ADMA/DDAH pathway.

• MeSH
• amidohydrolasy metabolismus   MeSH
• analýza buněčné migrace MeSH
• antigeny CD151 metabolismus   MeSH
• arginin analogy a deriváty   metabolismus   MeSH
• cévní endotel cytologie   MeSH
• cytokiny metabolismus   fyziologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   MeSH
• fyziologická neovaskularizace fyziologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• pohyb buněk fyziologie   MeSH
• proliferace buněk MeSH
• signální transdukce fyziologie   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• transfekce MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH