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Pravastatin-induced proangiogenic effects depend upon extracellular FGF-2.

Shiota M, Hikita Y, Kawamoto Y, Kusakabe H, Tanaka M, Izumi Y, Nakao T, Miura K, Funae Y, Iwao H - J. Cell. Mol. Med. (2012)

Bottom Line: Here, we hypothesized that FGF-2 contributes to the proangiogenic effect of statins.We found that pravastatin, a hydrophilic statin, induced phosphorylation of the FGF receptor (FGFR) in human umbilical vein endothelial cells.These observations indicate that pravastatin exerts proangiogenic effects in endothelial cells depending upon the extracellular FGF-2.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan. sio@med.osaka-cu.ac.jp

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eNOS phosphorylation requires the FGF-2/FGFR system. HUVECs were preincubated with FGF-2-neutralizing antibody or SU5402 for 1 hr, and then stimulated with pravastatin for 10 min. The phosphorylation of eNOS was analysed by immunoblotting. Results were similar in two other experiments. Prav: pravastatin; NA: neutralizing antibody; SU: SU5402.
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fig06: eNOS phosphorylation requires the FGF-2/FGFR system. HUVECs were preincubated with FGF-2-neutralizing antibody or SU5402 for 1 hr, and then stimulated with pravastatin for 10 min. The phosphorylation of eNOS was analysed by immunoblotting. Results were similar in two other experiments. Prav: pravastatin; NA: neutralizing antibody; SU: SU5402.

Mentions: Statins induce Akt-mediated phosphorylation of eNOS at Ser1177, which results in nitric oxide production, but with no accompanying change in the total level of eNOS protein. To determine whether the activation of the eNOS by pravastatin depends on FGFR phosphorylation, quiescent HUVECs were stimulated with pravastatin in the absence or the presence of FGF-2-neutralizing antibody (5 μg/ml) or SU5402 (10 μM). Pravastatin induced eNOS phosphorylation at 10 min., whereas pretreatment of ECs with FGF-2-neutralizing antibody or SU5402 completely inhibited pravastatin-induced eNOS phosphorylation (Fig. 6).


Pravastatin-induced proangiogenic effects depend upon extracellular FGF-2.

Shiota M, Hikita Y, Kawamoto Y, Kusakabe H, Tanaka M, Izumi Y, Nakao T, Miura K, Funae Y, Iwao H - J. Cell. Mol. Med. (2012)

eNOS phosphorylation requires the FGF-2/FGFR system. HUVECs were preincubated with FGF-2-neutralizing antibody or SU5402 for 1 hr, and then stimulated with pravastatin for 10 min. The phosphorylation of eNOS was analysed by immunoblotting. Results were similar in two other experiments. Prav: pravastatin; NA: neutralizing antibody; SU: SU5402.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3822970&req=5

fig06: eNOS phosphorylation requires the FGF-2/FGFR system. HUVECs were preincubated with FGF-2-neutralizing antibody or SU5402 for 1 hr, and then stimulated with pravastatin for 10 min. The phosphorylation of eNOS was analysed by immunoblotting. Results were similar in two other experiments. Prav: pravastatin; NA: neutralizing antibody; SU: SU5402.
Mentions: Statins induce Akt-mediated phosphorylation of eNOS at Ser1177, which results in nitric oxide production, but with no accompanying change in the total level of eNOS protein. To determine whether the activation of the eNOS by pravastatin depends on FGFR phosphorylation, quiescent HUVECs were stimulated with pravastatin in the absence or the presence of FGF-2-neutralizing antibody (5 μg/ml) or SU5402 (10 μM). Pravastatin induced eNOS phosphorylation at 10 min., whereas pretreatment of ECs with FGF-2-neutralizing antibody or SU5402 completely inhibited pravastatin-induced eNOS phosphorylation (Fig. 6).

Bottom Line: Here, we hypothesized that FGF-2 contributes to the proangiogenic effect of statins.We found that pravastatin, a hydrophilic statin, induced phosphorylation of the FGF receptor (FGFR) in human umbilical vein endothelial cells.These observations indicate that pravastatin exerts proangiogenic effects in endothelial cells depending upon the extracellular FGF-2.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan. sio@med.osaka-cu.ac.jp

Show MeSH