The role of phosphoinositide 3-kinase (PI3K) in mediating mitogen and Simvastatin induced effects in the vasculature
Statins induce beneficial vascular effects. How statins induce beneficial vascular effects is yet to be determined. Here we examine Simvastatin and vascular endothelial growth factor (VEGF) acting through the phosphoinositide 3-kinase (PI3K) pathway in human coronary artery endothelial cells (HCAEC). While Simvastatin and VEGF both activated mediators in the PI3K pathway, the proteins and the rates of activation were not always consistent. This suggests that although Simvastatin and VEGF share a common PI3K pathway in HCAEC and similar vascular effects, the agonists diverge in the induction of cellular signaling cascades. Simvastatin also was shown to induce phosphoinositide 3, 4, 5-triphosphate (PIPS) organization and PI3K p110 gamma (y) perinuclear localization. Beneficial, non-lipid lowering effects of statins may occur through the PI3K pathway through activation of distinct mediators from those of VEGF. Better understanding of the pathways associated with statins is necessary for the discovery of better treatments for cardiovascular disease (CVD).