Tirofiban Positively Regulates β1 Integrin and Favours Endothelial Cell Growth on Polylactic Acid Biopolymer Vascular Scaffold (BVS)

J Cardiovasc Transl Res. 2018 Jun;11(3):201-209. doi: 10.1007/s12265-018-9805-1. Epub 2018 Apr 25.

Abstract

An unexpectedly high incidence of thrombosis in patients that received the polylactic acid bioresorbable vascular scaffold (BVS) suggests a delayed/incomplete endothelial repair with this stent. The anti-platelet agent tirofiban stimulates endothelial cell migration and proliferation, mediated by VEGF production. We investigated the tirofiban effect on the migration and adhesion of endothelial cells to BVS, in vitro. We performed human umbilical endothelial cell (HUVEC) cultures in the presence of BVS. Tirofiban, similarly to VEGF, increased the ability of HUVEC to grow on the vascular scaffold, compared to unstimulated or abciximab-treated cells. Tirofiban increased HUVEC expression of β1 and β3 integrins along with collagen and fibronectin. A role for β1 integrin in the "pro-adhesive and -migratory" signals elicited by tirofiban was suggested by use of an anti-β1-blocking antibody that prevented poly-levo-lactic acid vascular scaffold colonization. Our study suggests that tirofiban may improve the outcomes of patients receiving BVS by accelerating stent endothelization.

Keywords: Adhesion; BVS; Migration; Tirofiban; β1 integrin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab / pharmacology
  • Absorbable Implants*
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Collagen / metabolism
  • Fibronectins / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Integrin beta1 / metabolism*
  • Integrin beta3 / metabolism
  • Percutaneous Coronary Intervention / instrumentation*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Polyesters / chemistry*
  • Prosthesis Design
  • Re-Epithelialization / drug effects*
  • Signal Transduction / drug effects
  • Stents*
  • Tirofiban / pharmacology*
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Fibronectins
  • ITGB3 protein, human
  • Integrin beta1
  • Integrin beta3
  • Platelet Aggregation Inhibitors
  • Polyesters
  • Vascular Endothelial Growth Factor A
  • poly(lactide)
  • Collagen
  • Tirofiban
  • Abciximab