Atorvastatin Accelerates Both Neointimal Coverage and Re-Endothelialization After Sirolimus-Eluting Stent Implantation in a Porcine Model

– New Findings From Optical Coherence Tomography and Pathology –

Abstract

Background: Delayed vessel healing after drug-eluting stent implantation is thought to be the underlying mechanisms of late stent thrombosis (LST). Methods and Results: In the animal model of stenting, 45 minipigs were divided into 3 groups (n=15 each): bare metal stent (BMS), sirolimus-eluting stent (SES), and SES plus atorvastatin treatment (SES+ator). Neointimal coverage and endothelium coverage were evaluated separately by optical coherence tomography (OCT), pathology, and scanning electron microscopy (SEM) at days 7, 14 and 28. OCT showed that SES significantly delayed neointimal coverage compared with BMS and the percentage of uncovered struts in the SES+ator group was significantly decreased on days 7 (42.7±1.3% vs. 56.8±5.7%, P<0.01) and 14 (24.8±4.3% vs. 45.3±2.8%, P<0.01) compared with the SES group. However, re-endothelialization was even more seriously delayed than neointima formation after SES deployment (P<0.05). Pathology and SEM revealed improved re-endothelialization of the neointima with atorvastatin therapy in terms of more struts covered by endothelium, less platelet adhesion, and higher endothelial nitric oxide synthase expression of the endothelial cells in the SES+ator group. Flow cytometry illustrated that the SES+ator group had more mobilized endothelial progenitor cells (EPCs) compared with the SES group at day 7 (0.21±0.02% vs. 0.11±0.03%, P=0.022). Conclusions: Atorvastatin pretreatment can accelerate both neointimal coverage and re-endothelialization after SES implantation, which may be mediated by the mobilization of EPC and enhancement of the endothelial function of the neointima.  (Circ J 2012; 76: 2561–2571)