Investigating the Putative Mechanism and Functional Role of RGS5 Upregulation in Vascular Smooth Muscle Cells Following Statin Treatment

RGS5 within vascular smooth muscle cells (VSMCs) is capable of inhibiting G-protein signaling involved in VSMC recruitment. Based on the suggested ability of statin to upregulate RGS5, we investigated whether RGS5 could mediate the pleiotropic effects of statins in VSMCs. Fluvastatin treatment of isolated VSMCs significantly increased the expression of RGS5, while downregulating RGS2, RGS3, and RGS16. However, these results were not observed ex vivo or in vivo within the aorta following fluvastatin treatment. Fluvastatin also upregulated PPARδ and PPARγ, demonstrated transcriptional regulators of RGS5 expression, in VSMCs. However, PPARδ and PPARγ antagonists did not block fluvastatin-induced RGS5 upregulation and their agonists did not increase RGS5 expression. Lastly, fluvastatin did not significantly reduce neointimal hyperplasia following femoral artery injury in RGS5 WT and KO mice. These results suggest that statins robustly upregulate RGS5 only in cultured synthetic VSMCs, with the physiological role of this pleiotropic effect remaining to be elucidated.M.Sc