Abstract
Currently available drug-eluting stents have been shown to reduce the prevalence of in-stent restenosis. However, their use is limited by their enormous cost and unwanted side effects associated with both drugs, sirolimus and paclitaxel, presently used to coat most of the stents clinically avilable. Due to their lack of selectivity with respect to targeted cell types these drugs do not only inhibit vascular smooth muscle cell proliferation underlying neointima formation, they also compromise endothelial repair increasing the risk for subacute thrombosis following implantation of drug-eluting stents. Accordingly, there is need for new costeffective agents capable to inhibit restenosis without clinically relevant, unwanted side effects. In the present paper a selection of the most important patent applications published within the last 3 years and claiming the use of homologous cellular and extracellular agents as therapeutics or targets to prevent restenosis are reviewed. Such agents include c-Jun, the focal adhesion kinase (FAK) and its inhibitor FAK-related non-kinase (FRNK), estrogen receptors, variants of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) as well as some so far poorly characterized factors supposedly involved in the control of cell proliferation, inflammation and apoptosis. Such agents promise to be cost-effective and, in some cases, potentially devoid of unwanted side effects. Clinical long-term studies have yet to support such notions.
Keywords: Restenosis, neointima, angioplasty, drug-eluting stent, endothelial repair, vascular smooth muscle cells, subacute thrombosis, vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), protein associated with restenosis inhibition and secreted (PARIS), focal adhesion kinase (FAK), focal adhesion kinase-related non-kinase (FRNK), c-Jun, estrogen receptors, cost-effectiveness
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