Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis.
Synthetic polymers, like methacrylate (MA) compounds, have been clinically introduced as inert coatings to locally deliver drugs that inhibit restenosis after stent. The aim of the present study was to evaluate the effects of MA coating alone on vascular smooth muscle cell (VSMC) growth in vitro. Stainless steel stents were coated with MA at the following doses: 0.3, 1.5, and 3 ml. Uncoated/bare metal stents were used as controls. VSMCs were cultured in dishes, and a MA-coated stent or an uncoated bare metal stent was gently added to each well. VSMC proliferation was assessed by bromodeoxyuridine (BrdU) incorporation. Apoptosis was analyzed by three distinct approaches: 1) annexin V/propidium iodide fluorescence detection; 2) DNA laddering; and 3) caspase-3 activation and PARP cleavage. MA-coated stents induced a significant decrease of BrdU incorporation compared with uncoated stents at both the low and high concentrations. In VSMCs incubated with MA-coated stents, annexin V/propidium iodide fluorescence detection showed a significant increase in apoptotic cells, which was corroborated by the typical DNA laddering. Apoptosis of VSMCs after incubation with MA-coated stents was characterized by caspase-3 activation and PARP cleavage. The MA-coated stent induced VSMC growth arrest by inducing apoptosis in a dose-dependent manner. Thus MA is not an inert platform for eluting drugs because it is biologically active per se. This effect should be taken in account when evaluating an association of this coating with antiproliferative agents for in-stent restenosis prevention.
Curcio
Antonio
A
Div. of Cardiology, Dept. of Experimental and Clinical Medicine, Magna Graecia Univ., Via Tommaso Campanella 115, 88100 Catanzaro, Italy.
Torella
Daniele
D
Cuda
Giovanni
G
Coppola
Carmela
C
Faniello
Maria Concetta
MC
Achille
Francesco
F
Russo
Viviana G
VG
Chiariello
Massimo
M
Indolfi
Ciro
C
D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D066298:In Vitro Techniques; D008689:Methacrylates / Q000378:metabolism / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D015607:Stents
D020099:Coated Materials, Biocompatible; D008689:Methacrylates