Abstract 3737: Development of the New Gene-Eluting Stent that Prevents Subacute In-Stent Thrombosis by Enhancing E-NTPDase Activity in Injured Artery
Stent thrombosis has been feared after coronary intervention with the current coronary stents. ADP plays a key role in platelet aggregation also in stent thrombosis. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) rapidly hydrolyzes ADP to AMP, thereby inhibiting platelet aggregation. We investigated whether human placental E-NTPDase (hE-NTPDase) gene transfer by the cationized gelatin-coated stent (GCS) into injured artery could prevent subacute stent thrombosis without the use of antiplatelet drugs. We generated pBS CAG vectors encoding hE-NTPDase and GCS for gene transfer. We used 52 male Japanese white rabbits weighing 2.3 to 2.5 kg. All rabbits underwent the repeated balloon injury of right femoral artery (FA) at 4-week intervals to induce the platelet-rich thrombi. The rabbits were divided into four groups according to the implanted stent: the bare metal stent (BMS) group, the GCS group, the Lac Z gene eluting stent (LacZ stent) group, and the hE-NTPDase gene eluting stent (hE-NTPDase stent) group. Immediately after the second injury, the stents were implanted into injured FA. Patency was confirmed in all injured FA of the hE-NTPDase stent group by continuous Doppler and angiogram on day 3 and 7, and the patency rate was significantly lower in other 3 groups (17 to 50% p<0.05). The mRNA expression level of the endogenous E-NTPDase, which is an isoform of placental E-NTPDase and expressed in normal vascular endothelial cells, was dramatically reduced in injured FA. However, in the hE-NTPDase stent group, hE-NTPDase mRNA and its protein were detected in the stent implanted FA on day 3 and 7. NTPDase activity in the stent implanted FA on day 3 and 7 in the hE-NTPDase stent group was higher than that in the contralateral normal FA, and significantly higher than that in the stent implanted FA in the BMS group (P<0.05). Histological examination revealed the occlusion of the stent implanted FA with thrombus strongly immunopositive for GP IIbIIIa in the BMS and GCS groups but not in the hE-NTPDase stent group. E-NTPDase gene eluting stent can completely prevent subacute thrombosis in the injured artery without antiplatelet drugs.