Endothelial Barrier Protein Expression in Biodegradable Polymer Sirolimus-Eluting Versus Durable Polymer Everolimus-Eluting Metallic Stents

JACC Cardiovasc Interv. 2017 Dec 11;10(23):2375-2387. doi: 10.1016/j.jcin.2017.06.059. Epub 2017 Nov 1.

Abstract

Objectives: This study sought to investigate endothelial coverage and barrier protein expression following stent implantation.

Background: Biodegradable polymer drug-eluting stents (BP-DES) have been purported to have biological advantages in vessel healing versus durable polymer DES (DP-DES), although clinical trial data suggest equipoise.

Methods: Biodegradable polymer-sirolimus-eluting stents (BP-SES), durable polymer-everolimus-eluting stents (DP-EES), and bare-metal stents (BMS) were compared. In the rabbit model (28, 45, and 120 days), stented arteries underwent light microscopic analysis and immunostaining for the presence of vascular endothelium (VE)-cadherin, an endothelial barrier protein, and were subjected to confocal microscopy and scanning electron microscopy. A cell culture study in stented silicone tubes was performed to assess cell proliferation.

Results: Light microscopic assessments were similar between BP-SES and DP-EES. BMS showed nearly complete expression of VE-cadherin at 28 days, whereas both DES showed significantly less with results favoring BP-SES versus DP-EES (39% coverage in BP-SES, 22% in DP-EES, 95% in BMS). Endothelial cell morphologic patterns differed according to stent type with BMS showing a spindle-like shape, DP-EES a cobblestone pattern, and BP-SES a shape in between. VE-cadherin-negative areas showed greater surface monocytes regardless of type of stent. Cell proliferation was suppressed in both DES with numerically less suppression in BP-SES versus DP-EES.

Conclusions: This is the first study to examine VE-cadherin expression after DES. All DES demonstrated deficient barrier expression relative to BMS with results favoring BP-SES versus DP-EES. These findings may have important implications for the development of neoatherosclerosis in different stent types.

Keywords: VE-cadherin; biodegradable polymer; drug-eluting stent(s); durable polymer; endothelium.

Publication types

  • Comparative Study

MeSH terms

  • Absorbable Implants*
  • Animals
  • Antigens, CD / metabolism
  • Cadherins / metabolism
  • Cardiovascular Agents / administration & dosage*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Drug-Eluting Stents*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / ultrastructure
  • Endovascular Procedures / adverse effects
  • Endovascular Procedures / instrumentation*
  • Everolimus / administration & dosage*
  • Iliac Artery / drug effects*
  • Iliac Artery / metabolism
  • Iliac Artery / ultrastructure
  • Intercellular Junctions / drug effects*
  • Intercellular Junctions / metabolism
  • Intercellular Junctions / ultrastructure
  • Male
  • Metals / chemistry*
  • Models, Animal
  • Neointima
  • Polymers / chemistry*
  • Prosthesis Design
  • Rabbits
  • Sirolimus / administration & dosage*
  • Time Factors

Substances

  • Antigens, CD
  • Cadherins
  • Cardiovascular Agents
  • Metals
  • Polymers
  • cadherin 5
  • Everolimus
  • Sirolimus