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

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.

The integrin beta1 modulator Tirofiban prevents adipogenesis and obesity by the overexpression of integrin-linked kinase: a pre-clinical approach in vitro and in vivo

“…Although ILK activity may not be responsible for upstream INTB1 phosphorylation, our results indicate that an axis made up of ILK-AKT/GSK3β may be responsible for the downstream TF-mediated reduction of adipogenesis and hypertrophy. Some publications agree with this hypothesis: AKT and GSK3β are related to adipocyte differentiation [ 28 – 30 ] and, as we already demonstrated, cKDILK animals have reduced AKT phosphorylation in epiWAT, concomitantly with the downregulated ILK expression and the increased fat mass and insulin resistance [ 36 , 37 ] as well as TF depends on AKT to favor endothelial cell growth [ 42 , 43 ]. AKT/GSK3β showed phosphorylation after a longer period of TF treatment (16/24 h in vitro, 2 weeks of daily administration in vivo), in accordance with the observed increased expression of ILK, however, it is also probable that the repeated and long-time exposure of TF in vivo produces an indirect effect on AKT/GSK3β.…”

“…C3H10T1/2 preadipocytes (CCL-226, ATCC, Manassas, USA) [ 43 ] were grown on 6-well plates with DMEM (Sigma-Aldrich, St. Louis, MO, USA) and 10% fetal bovine serum (FBS, Thermo Fisher Scientific Waltham, MA, USA). 2 days after cells reached confluency, they were induced to differentiate with DMEM supplemented with 10% FBS and Glutamax (Thermo Fisher Scientific), 1 µM dexamethasone, 1 µM rosiglitazone, 0.5 mM 3-isobutyl-1-methylxanthine (IBMX, Sigma-Aldrich) and 5 µg/ml insulin (Merck, Sigma-Aldrich) for 48 h. Medium was replaced every two days for a total of 6–10 days with DMEM supplemented with Glutamax, 10% FBS and 5 µg/ml insulin.…”

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

“…Tirofiban was found to improve EC migration and proliferation in bioabsorbable stents using a HUVEC endothelial model [172]. Several studies in the HUVEC model have shown that coating stents with other polymers can reduce the risk of complications [173][174][175].…”

“…They are used as an alternative treatment for coronary artery obstruction. However, the two main complications of stent implantation are restenosis and thrombosis [110,171,172]. HUVEC models have been used to explore ways to prevent these complications.…”