Re-occlusion of blood vessels following percutaneous coronary intervention with stenting (in stent stenosis) occurs in 5–10% of patients receiving drug-eluting stents. Re-occlusion of the treated vessel is observed when vascular smooth muscle cells (VSMCs) proliferate and migrate in response to vessel injury, inflammation and impaired healing of the endothelial cell layer. Novel drug eluting stents that reduce inflammation and permit endothelial repair whilst preventing detrimental VSMC proliferation and migration might reduce the occurrence of in stent restenosis. We previously have shown that ibuprofen has differential effects on vascular smooth muscle and endothelial cell proliferation and migration and, thus, might be a promising drug to deliver in a novel drug eluting stent platform. We do not fully understand why vascular smooth muscle and endothelial cells respond differently to ibuprofen but hypothesise that ibuprofen is regulating VSM C proliferation and migration, at least in part, via a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent mechanism. In this study, we have used PPARγ agonists, troglitazone, pioglitazone, and rosiglitazone, to establish the role of PPARγ in the regulation of cell proliferation in the A10 VSMC cell line. Interestingly, whilst 50 µM and 100 µM troglitazone inhibited A10 VSMC proliferation by 58.9±4.6% and 21.6±4.8%, respectively, pioglitazone and rosiglitazone had no effect on VSMC cell proliferation at any concentrations tested. The observations that only one PPARγ agonist tested inhibited VSMC proliferation and that high concentrations of troglitazone were required to observe a significant effect (EC50=54.6 µM) suggest that troglitazone might be acting in a PPARγ-independent manner.
- CARDIAC PROCEDURES AND THERAPY
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