Effect of a Novel Stent on Re-Endothelialization, Platelet Adhesion, and Neointimal Formation

J Atheroscler Thromb. 2016;23(1):67-80. doi: 10.5551/jat.31062. Epub 2015 Sep 3.

Abstract

Aim: Vascular endothelial-cadherin (VE-cadherin) is specifically expressed by outgrowth endothelial cells (OECs). Zwitterionic stent showed high antifouling and excellent blood compatibility. Therefore, we hypothesized that anti-VE-cadherin antibody-coated zwitterionic stents (VE-cad-Z stents) would promote re-endothelialization, reduce neointimal formation, and resist thrombus.

Methods: VE-cad-Z stents were examined using platelet adhesion test, platelet activation, and OEC capture ability in vitro. In vivo effect of VE-cad-Z stents on re-endothelialization, thrombus-resistance, and neointima hyperplasia was investigated in left common carotid arteries of rabbits (n=15).

Results: In vitro, VE-cad-Z stents showed better platelet-resistance and OEC-capture ability (DNA concentration: 297.23±22.71 versus 67.49±15.26 ng/µL, P<0.01). In vivo, VE-cad-Z stents exhibited better patency rate than bare metal stents (BMS) (15/15 versus 12/15), and it significantly reduced platelet adhesion and neointima formation (neointima area: 1.13±0.05 versus 1.00±0.05mm(2), P<0.01 and 3.04±0.11versus 1.05±0.06mm(2), P<0.01, at 3 and 30 days, respectively; % stenosis: 20.99±0.98 versus 18.72±0.97, P<0.01 and 56.46±2.20 versus 19.45±1.24, P<0.01, at 3 and 30 days, respectively).

Conclusion: These data suggested that VE-cad-Z stents could specifically capture OECs, consequently promote endothelial healing, and also reduce platelet adhesion and neointima formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Blood Platelets / cytology*
  • Cadherins / metabolism*
  • Carotid Artery, Common / pathology
  • Cell Adhesion
  • Cell Proliferation
  • Drug-Eluting Stents*
  • Endothelial Cells / cytology
  • Endothelium, Vascular / pathology*
  • Humans
  • Hyperplasia / pathology
  • Inflammation
  • Male
  • Microscopy, Fluorescence
  • Neointima / pathology*
  • Platelet Activation
  • Platelet Adhesiveness*
  • Rabbits
  • Thrombosis / pathology

Substances

  • Antigens, CD
  • Cadherins
  • cadherin 5