Abstract 1962: Differential Response to Vascular Stenting in Control Vs Insulin-Treated Diabetic Pigs: Analysis of Carotid, Renal and Coronary Bare Metal Stents (BMS) and Coronary Sirolimus Eluting Stents (SES)

Background: Diabetes (DM) is consistently associated with increased cardiovascular disease risk and worse outcomes from revascularization including endovascular BMS and SES. We studied the response of coronary and peripheral arteries to SES and BMS in a unique insulin treated DM pig model. Methods and Results: controlled, chronic (9 wks) hyperglycemia was achieved in pigs after Streptozotocin induction and daily insulin injections. 30 coronary stents (18 BMS, 12 SES) and 22 peripheral stents (12 carotid, 10 renal, all BMS) were deployed in DM and control pigs. SES reduced neointimal proliferation in Controls, but not DM coronaries. DM pigs developed thicker neointima in response to carotid and renal stenting at 28-d (Figure A). Fibrin deposition and intimal neo-vascularization were increased while re-endothelialization blunted in DM. Stenting elicited increased vascular inflammation (CD-45 + tissue macrophages) across stented sites that correlated with neointimal response in DM but not controls (Figure B). DM pig vessels did exhibit altered signaling pathway activation with increased p-ERK (Thr202/Tyr204) and reduced p-Akt (Ser473) immunohistochemically stained cells; most prominently in stented peripheral arteries. Conclusions: In-stent carotid and renal neointimal proliferation is increased in insulin treated DM while the response to local drug elution in coronary stents is blunted. Chronic controlled hyperglycemia results in mechanistically and quantitatively varied neointimal proliferation that is vascular bed-specific.