Ibuprofen inhibits migration and proliferation of human coronary artery smooth muscle cells by inducing a differentiated phenotype: role of peroxisome proliferator-activated receptor γ.
OBJECTIVE
The search for agents that are capable of preventing restenosis and reduce the risk of late thrombosis is of utmost importance. In this study we aim to evaluate the in vitro effects of ibuprofen on proliferation and migration of human coronary artery smooth muscle cells and on endothelial cells.


METHODS
Cell proliferation was evaluated by trypan blue exclusion. Cell migration was assessed by wound-healing 'scratch' assay and time-lapse video microscopy. Protein expression was assessed by immunoblotting, and morphology by immunocytochemistry. The involvement of the PPARγ pathway was studied with the agonist troglitazone, and the use of selective antagonists such as PGF2α and GW9662.


RESULTS
We demonstrate that ibuprofen inhibits proliferation and migration of HCASMCs and induces a switch in HCASMCs towards a differentiated and contractile phenotype, and that these effects are mediated through the PPARγ pathway. Importantly we also show that the effects of ibuprofen are cell type-specific as it does not affect migration and proliferation of endothelial cells.


CONCLUSIONS
Taken together, our results suggest that ibuprofen could be an effective drug for the development of novel drug-eluting stents that could lead to reduced rates of restenosis and potentially other complications of DES implantation.
School of Pharmacy, University of Reading, Reading, UK; Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, UK.
Abeer
A
Dannoura
Alejandro
A
Giraldo
Ines
I
Pereira
Jonathan M
JM
Gibbins
Phil R
PR
Dash
Katrina A
KA
Bicknell
Gavin
G
Brooks
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology*; D010641:Phenotype
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047495:PPAR gamma; D007052:Ibuprofen
CAD; DES; NSAIDs; PCI; PPAR; coronary artery disease; drug-eluting stent; nonsteroidal antinflammatory drugs; percutaneous coronary intervention; peroxisome proliferator-activated receptor