Abstract:
:A rat sponge implant model was used to examine the role of protein kinase C (PKC) in angiogenesis. Neovascular response was determined by measurements of relative sponge blood flow by a 133Xe clearance technique and confirmed histologically. Morphometric analysis was used to quantitate the amount of fibrovascular growth in the sponges. Daily doses of recombinant human basic fibroblast growth factor (bFGF, 100 ng), tumor necrosis factor-alpha (TNF-alpha, 50 ng), or interleukin-1-alpha (IL-1 alpha, 50 ng) caused neovascular responses that were blocked by daily coadministration of the selective PKC inhibitor, calphostin C (4 micrograms). To confirm that calphostin C was able to inhibit PKC in vivo, its effect on the angiogenic response elicited by the PKC activator, phorbol 12-myristate 13-acetate (PMA, 30 micrograms) was examined. The blood flow and morphometric data clearly showed that the intense neovascularization induced by PMA was totally suppressed by coadministration of calphostin C (4 micrograms). Thus, these results suggest that cytokine-induced angiogenesis may be mediated in part through the activation of PKC and that selective inhibition of this enzyme could have therapeutic benefit in angiogenic diseases.
journal_name
Inflammationjournal_title
Inflammationauthors
Hu DE,Fan TPdoi
10.1007/BF01534379subject
Has Abstractpub_date
1995-02-01 00:00:00pages
39-54issue
1eissn
0360-3997issn
1573-2576journal_volume
19pub_type
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