Author + information
- Emanuel Harari,
- Frank Kolodgie,
- Liang Guo,
- Eduardo Acampado,
- Matthew Kutyna,
- Hiroyoshi Mori,
- Samantha Smith,
- Aloke Finn and
- Renu Virmani
Background: DES increase neoatherosclerosis (NA) compared to BMS. The mechanism of NA remains elusive. mTOR inhibitors in DES prevent proliferation of SMC but affects endothelial cells (EC). VE-Cadherin (VE-CAD) maintains the integrity of EC junctions. We hypothesize that DES affects the EC via VE-CAD. Increased permeability enables monocyte and LDL to transverse the endothelium and form a plaque. Torin-2 an mTor inhibitor with less effect on VE-CAD, might be less prone to NA.
Methods: NZW Rabbits underwent denudation in the iliac arteries and were implanted with BMS, Everolimus or Torin-2 DES. At 60 days the rabbits were injected with Evans Blue (EB) to demonstrated permeability and sacrificed. Imaging with VE-CAD and p120 antibodies was performed. Coverage was assessed by SEM. Permeability was assessed by Transendothelial Electrical Resistance (TEER) in HUVECs.
Results: EB shows increased permeability with patches of functional endothelium in the DES vs. BMS. BMS showed VE CAD coverage, while in DES there was a patchy pattern that corresponded to lack of EB. On high magnification BMS shows a pattern of high VECAD/p120 colocalization. DES exhibit areas of high and low co-localization. TEER measurement confirmed low resistance with Everolimous and Intermediate with Torin vs. control.
Conclusions: DES induce EC dysfunction 60 days after implant, with abnormal VE-CAD/p120. This pattern may increased permeability and NA. Torin-2, a selective mTor inhibitor shows improved EC function and may decrease NA.
Moderated Poster Contributions
Interventional Cardiology Moderated Poster Theater, Poster Hall, Hall C
Friday, March 17, 2017, 11:45 a.m.-11:55 a.m.
Session Title: Refining PCI Technique and Outcomes
Abstract Category: 25. Interventional Cardiology: Translation and Pre-clinical Research
Presentation Number: 1135M-17
- 2017 American College of Cardiology Foundation