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Serum amyloid A stimulates cultured endothelial cells to migrate and proliferate: inhibition by the multikinase inhibitor BIBF 1120
Author(s) -
Cai Xiaoping,
Freedman S Ben,
Witting Paul K
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12148
Subject(s) - endothelial stem cell , chemistry , serum amyloid a , proinflammatory cytokine , tumor necrosis factor alpha , vascular endothelial growth factor , endocrinology , angiogenesis , medicine , microbiology and biotechnology , inflammation , biology , biochemistry , in vitro , vegf receptors
Summary In the present study, we tested whether serum amyloid A ( SAA ) protein, an established biomarker of inflammation, also plays a role in stimulating neovascularization. To evaluate this possibility, human carotid artery endothelial ( HC t AE ) cells were cultured and cellular migration and the proinflammatory and/or thrombotic activity of SAA (0, 1 or 10 μg/mL) on vascular endothelial cells was verified by determining gene regulation relative to control (in the absence of SAA ). Exposure of HC t AE cells to SAA increased expression of the transcription factor nuclear factor‐κ B ( NFKB ), tumour necrosis factor ( TNF ) and pro‐coagulative tissue factor ( F 3 ), and stimulated phosphorylation of the P 65 subunit of the NFKB complex. Enhanced production of TNF and NFKB was paralleled by increased vascular endothelial growth factor ( VEGF ) m RNA and protein expression, as demonstrated by quantitative polymerase chain reaction, western blotting and ELISA . Administration of 10 μg/mL SAA enhanced endothelial cell migration (1.6‐fold vs control), stimulated regrowth of HC t AE cells after mechanical injury (˜1.2‐fold vs control) and increased endothelial tube formation relative to control after 6 h. The SAA ‐mediated enhancement of endothelial cell migration, proliferation and tube formation were markedly inhibited by pretreatment of HC t AE cells with the multi‐angiokinase receptor inhibitor BIBF 1120 (100 nmol/L), although SAA ‐stimulated gene responses for F 3 and NFKB were unaffected by 100 nmol/L BIBF 1120 pretreatment. Overall, BIBF 1120 inhibited the pro‐angiogenic activity of SAA on vascular endothelial cells in this experimental model of inflammation.