Pravastatin-induced proangiogenic effects depend upon extracellular FGF-2

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Endothelial Cell Biology

Background:

• HMG-CoA reductase inhibitors (statins) offer vascular protection beyond cholesterol reduction, including promoting angiogenesis.
• The proangiogenic effects of statins are linked to PI3K/Akt pathway activation in endothelial cells, but the precise mechanism remains unclear.

Purpose of the Study:

• To investigate the role of fibroblast growth factor-2 (FGF-2) in mediating the proangiogenic effects of statins, specifically pravastatin.
• To elucidate the signaling pathway through which pravastatin activates endothelial cells.

Main Methods:

• Human umbilical vein endothelial cells were treated with pravastatin.
• Phosphorylation of FGF receptor (FGFR), Akt, and MAPK was assessed.
• FGFR inhibitor (SU5402) and anti-FGF-2 antibodies were used to block signaling.
• Extracellular FGF-2 was depleted using heparin.
• Endothelial cell proliferation, migration, and tube formation assays were performed.

Main Results:

• Pravastatin induced FGFR phosphorylation in endothelial cells.
• FGFR inhibition abolished pravastatin-induced Akt and MAPK activation.
• Anti-FGF-2 antibodies blocked pravastatin-mediated Akt and MAPK activity.
• Heparin-induced depletion of FGF-2 prevented pravastatin's effects on Akt and MAPK.
• Blocking FGF-2 inhibited pravastatin-enhanced endothelial cell proliferation, migration, and tube formation.

Conclusions:

• Pravastatin's proangiogenic effects in endothelial cells are dependent on extracellular FGF-2.
• Pravastatin activates the PI3K/Akt and MAPK pathways via FGFR signaling, mediated by FGF-2.
• This study reveals a novel mechanism for statin-induced angiogenesis involving the FGF-2/FGFR axis.