Abstract

BackgroundNeointima forming after stent implantation consists of vascular smooth muscle cells (VSMCs) in 90%. Growth factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A play an important role in VSMC proliferation and migration to the tunica intima after arterial wall injury. The aim of this paper was an analysis of functional polymorphisms in genes encoding TGF-β1, PDGFB, EGF, bFGF and VEGF-A in relation to in-stent restenosis (ISR).Materials and Methods265 patients with a stable coronary artery disease (SCAD) hospitalized in our center in the years 2007–2011 were included in the study. All patients underwent stent implantation at admission to the hospital and had another coronary angiography performed due to recurrence of the ailments or a positive result of the test assessing the coronary flow reserve. Angiographically significant ISR was defined as stenosis >50% in the stented coronary artery segment. The patients were divided into two groups–with angiographically significant ISR (n = 53) and without significant ISR (n = 212). Additionally, the assessment of late lumen loss (LLL) in vessel was performed. EGF rs4444903 polymorphism was genotyped using the PCR-RFLP method whilst rs1800470 (TGFB1), rs2285094 (PDGFB) rs308395 (bFGF) and rs699947 (VEGF-A) were determined using the TaqMan method.ResultsAngiographically significant ISR was significantly less frequently observed in the group of patients with the A/A genotype of rs1800470 polymorphism (TGFB1) versus patients with A/G and G/G genotypes. In the multivariable analysis, LLL was significantly lower in patients with the A/A genotype of rs1800470 (TGFB1) versus those with the A/G and G/G genotypes and higher in patients with the A/A genotype of the VEGF-A polymorphism versus the A/C and C/C genotypes. The C/C genotype of rs2285094 (PDGFB) was associated with greater LLL compared to C/T heterozygotes and T/T homozygotes.ConclusionsThe polymorphisms rs1800470, rs2285094 and rs6999447 of the TGFB1, PDGFB and VEGF-A genes, respectively, are associated with LLL in patients with SCAD treated by PCI with a metal stent implantation.

Highlights

  • ObjectivesThe aim of this paper was an analysis of functional polymorphisms in genes encoding TGFβ1, PDGFB, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGF-A) in relation to in-stent restenosis (ISR)

  • Neointima forming after stent implantation consists of vascular smooth muscle cells (VSMCs) in 90%

  • late lumen loss (LLL) was significantly lower in patients with the A/A genotype of rs1800470 (TGFB1) versus those with the A/G and G/G genotypes and higher in patients with the A/A genotype of the vascular endothelial growth factor A (VEGF-A) polymorphism versus the A/C and C/C genotypes

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Summary

Objectives

The aim of this paper was an analysis of functional polymorphisms in genes encoding TGFβ1, PDGFB, EGF, bFGF and VEGF-A in relation to in-stent restenosis (ISR). The roles of these growth factors [3–8] in restenosis are known, only one paper has described the role of TGFB1 gene polymorphisms in restenosis, whereas the roles of functional polymorphisms in the genes encoding PDGFB, bFGF, EGF and VEGF-A in restenosis have not been studied. The aim of this paper was to analyse the

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