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Low-dose quinacrine reduces vascular restenosis without affecting re-endothelialization

Low-dose quinacrine reduces vascular restenosis without affecting re-endothelialization

Authors :
Perrino, C.
Gargiulo, G.
Schiattarella, G. G.
Di Serafino, L.
Gianluigi Pironti
Magliulo, F.
Ilardi, F.
Serino, F.
Bottino, R.
Laurino, F. I.
Ferrone, M.
Bevilacqua, M.
Cirillo, P.
Indolfi, C.
Trimarco, B.
Esposito, G.
Perrino, Cinzia
Gargiulo, Giuseppe
Schiattarella, Gabriele Giacomo
Di Serafino, Luigi
Pironti, Gianluigi
Magliulo, Fabio
Ilardi, Federica
Serino, Federica
Bottino, Roberta
Laurino, FLORA ILARIA
Ferrone, Marco
Bevilacqua, Michele
Cirillo, Plinio
Indolfi, Ciro
Trimarco, Bruno
Esposito, Giovanni
Source :
Scopus-Elsevier

Abstract

Background: Coronary drug-eluting stents have significantly reduced the rate of in-stent restenosis, but the rate of in-stent thrombosis seems increased. In this study, we tested whether Quinacrine (Q) might reduce smooth muscle cells (SMC) proliferation while exerting minor effects on endothelial cells proliferation (EC) or thrombosis. Methods: Human SMC and EC were treated with increasing concentrations of Q, and the effects on apoptosis or cell proliferation were tested. Next, we evaluated Q effects on tissue factor (TF) and cell adhesion molecules expression (CAMs) in EC. Finally, we tested Q effects on neointima formation and re-endothelialization in a rat model of carotid artery angioplasty. Results: In SMC, all tested Q concentrations reduced proliferation, increased p53 expression and apoptosis. In contrast, EC, pro-apoptotic effects and TF activation were only observed after prolonged treatment with the highest dose, while CAMs expression was never induced at all concentrations. In vivo, Q induced p53 levels and apoptosis in the neointima, and significantly reduced neointimal formation without affecting re-endothelialization. Conclusion: Q exerts pro-apoptotic effects with higher selectivity for SMC, without pro-thrombotic effects, and might represent a safer drug to prevent or treat artery restenosis after percutaneous interventions.

Details

Database :
OpenAIRE
Journal :
Scopus-Elsevier
Accession number :
edsair.dedup.wf.001..23e74eecd517168d757c320963f8afd0