Bare metal stents increase mitogenic receptor gene expression in coronary artery of Ossabaw pig model of the metabolic syndrome

Ossabaw miniature swine are a large animal model of the metabolic syndrome because of the insulin resistance of lean Ossabaws and predisposition to obesity compared to other breeds (e.g. Yucatan). Our lab previously showed that P2Y2 and adenosine A1 receptors mediate proliferation of coronary smooth muscle cells. We hypothesized that bare metal coronary stents would induce P2Y2 and A1 receptor gene expression in this humanoid model. The circumflex (CFX) and left anterior descending (LAD) artery of male Ossabaws were stented at 1.0 or 1.3x lumen diameter by random assignment. Right coronary artery (RC, N=6) served as a non‐stented control. Pigs were sacrificed 4 wks after stenting. We assessed P2Y2 and A1 gene expression using real‐time RT‐PCR. Bare metal stents at 1.0x diameter did not affect P2Y2 expression (N=5). However, overinflation to 1.3x diameter strongly upregulated P2Y2 (~10 fold of unstented RC; N=5, p=0.05). There was also a significant (p=0.04, ANOVA) main treatment effect of stent deployment to increase A1 expression. CONCLUSION upregulation of P2Y2 and A1 receptor expression may contribute to in‐stent restenosis in the setting of the metabolic syndrome. Support: NIH RR13223, HL62552, ADA.