Effect of anti-ApoA-I antibody-coating of stents on neointima formation in a rabbit balloon-injury model

PLoS One. 2015 Mar 30;10(3):e0122836. doi: 10.1371/journal.pone.0122836. eCollection 2015.

Abstract

Background and aims: Since high-density lipoprotein (HDL) has pro-endothelial and anti-thrombotic effects, a HDL recruiting stent may prevent restenosis. In the present study we address the functional characteristics of an apolipoprotein A-I (ApoA-I) antibody coating in vitro. Subsequently, we tested its biological performance applied on stents in vivo in rabbits.

Materials and methods: The impact of anti ApoA-I- versus apoB-antibody coated stainless steel discs were evaluated in vitro for endothelial cell adhesion, thrombin generation and platelet adhesion. In vivo, response to injury in the iliac artery of New Zealand white rabbits was used as read out comparing apoA-I-coated versus bare metal stents.

Results: ApoA-I antibody coated metal discs showed increased endothelial cell adhesion and proliferation and decreased thrombin generation and platelet adhesion, compared to control discs. In vivo, no difference was observed between ApoA-I and BMS stents in lumen stenosis (23.3±13.8% versus 23.3±11.3%, p=0.77) or intima surface area (0.81±0.62 mm2 vs 0.84±0.55 mm2, p=0.85). Immunohistochemistry also revealed no differences in cell proliferation, fibrin deposition, inflammation and endothelialization.

Conclusion: ApoA-I antibody coating has potent pro-endothelial and anti-thrombotic effects in vitro, but failed to enhance stent performance in a balloon injury rabbit model in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Apolipoprotein A-I / immunology*
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Female
  • Homeostasis / drug effects
  • Humans
  • Microvessels / cytology
  • Neointima / metabolism
  • Neointima / pathology
  • Neointima / physiopathology
  • Neointima / prevention & control*
  • Platelet Adhesiveness / drug effects
  • Rabbits
  • Stents*
  • Surface Properties
  • Thrombin / biosynthesis

Substances

  • Antibodies, Monoclonal
  • Apolipoprotein A-I
  • Thrombin

Grants and funding

This work was supported by a grant from OrbusNeich Medical, Leek, The Netherlands, and supported in part by a grant from the Dutch Heart association (2008B070). OrbusNeich and the Dutch Heart association had no role in the study design, the collection, analysis and interpretation of the data, and in the writing of the report. Authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.