Recently Patented Applications of Homologous Cellular and Extracellular Agents as Therapeutics or Targets for the Prevention of Restenosis Post- Angioplasty

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 available. 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 cost-effective 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.

Vascular Injury Involves the Overoxidation of Peroxiredoxin Type II and Is Recovered by the Peroxiredoxin Activity Mimetic That Induces Reendothelialization

“…To prevent this poor prognosis, there is a medical need for agents with differential effects on VSMCs and VECs by which they circumvent the thrombotic problem. 3,4 The ETPs successfully reduced neointimal hyperplasia and simultaneously induced reendothelialization in the injured vessels. This evidence supports the therapeutic usefulness of ETPs as the coating materials for drug-eluting stents.…”

“…Therefore, the repair of the injured vasculature requires the inhibition of SMC hyperplasia and simultaneous induction of endothelialization. 3,4 Given that the platelet-derived growth factor receptor-β (PDGFRβ) and vascular endothelial growth factor receptor-2 (VEGFR2) are major receptor tyrosine kinases (RTKs) orchestrating the proliferation, chemotactic migration, and survival of VSMCs and VECs, respectively, 5,6 the coordinated control of these similar RTKs is essential for restoration of the injured arterial vessels.…”