Involvement of matrix metalloproteinase-9 in platelet-activating factor-induced angiogenesis

• Published in: FEBS letters Vol. 579; no. 11; pp. 2369 - 2375
• Main Authors: Ko, Hyun-Mi, Park, Yeong-Min, Jung, Bongnam, Kim, Han-A, Choi, Jung-Hwa, Park, Sung Jun, Lee, Hern-Ku, Im, Suhn-Young
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 25-04-2005
• Subjects: Animals; Cells, Cultured; Enzyme Inhibitors - pharmacology; Female; Gene Expression Regulation - drug effects; Humans; Matrix metalloproteinase; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred BALB C; MMP; Neovascularization, Physiologic - drug effects; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB; p65 antisense oligonucleotide; p65 AS; p65 nonsense scrambled oligonucleotide; p65 NS; PAF; Platelet Activating Factor - antagonists & inhibitors; Platelet Activating Factor - pharmacology; Platelet-activating factor; porcine pulmonary arterial endothelial cell; PPAEC; Promoter Regions, Genetic - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Swine; MMP; NF-κB; p65 AS; PPAEC; PAF; Platelet-activating factor; p65 NS; Matrix metalloproteinase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.03.035

Platelet-activating factor (PAF) augments angiogenesis by promoting the synthesis of various angiogenic factors, via the activation of NF-κB. In this study, we investigated the role of the matrix metalloproteinase (MMP)-9, in PAF-induced angiogenesis. PAF increased mRNA expression, protein synthesis, and MMP-9 activity in ECV304 cells, in a NF-κB-dependent manner. PAF increased MMP-9 promoter activity in ECV304, which was inhibited by WEB2107, and NF-κB inhibitors. Transfected NF-κB subunits, p65 or/and p50, increased luciferase activity in the reporter plasmid MMP-9, resulting in an increase not only of MMP-9 luciferase activity, but also of mRNA expression in MMP-9. MMP-9 or NF-κB inhibitors significantly inhibited PAF-induced angiogenesis, in a dose-dependent manner, in an in vivo mouse Matrigel implantation model. In a parallel to the Matrigel implantation study, MMP-9 or NF-κB inhibitors inhibited PAF-induced sprouting of porcine pulmonary arterial endothelial cells. These data indicate that NF-κB-dependent MMP-9 plays a key role in PAF-induced angiogenesis.