The Relationships between Polymorphisms in Genes Encoding the Growth Factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A and the Restenosis Process in Patients with Stable Coronary Artery Disease Treated with Bare Metal Stent

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.

Role of Gene Polymorphisms/Haplotypes and Plasma Level of TGF-β1 in Susceptibility to In-Stent Restenosis Following Coronary Implantation of Bare Metal Stent in Chinese Han Patients

“…Our findings partially agreed with Osadnik, et al, 33) who had reported that the C allele of the TGF-β1 869T/C polymorphism was associated with an increased risk of ISR only in dominant models (TC+CC versus TT) in the Polish population with stable CAD treated by PCI with BMS implantation. However, in our study, we found that the C allele of the TGF-β1 869T/C polymorphism was linked to an increased risk of ISR after coronary implantation of BMS in both additive (Per each C allele) and dominant (TC+CC versus TT) models in Chinese Han patients with CAD.…”

“…Current studies have examined the relationship between TGF-β1 polymorphisms and ISR. [32][33][34] However, none of the TGF-β1 genetic variations has ever been studied in relation to the risk of ISR after BMS implantation in the Chinese Han population. In the present study, we observed that Cdominant CC/CT genotype frequency of TGF-β1 869T/C polymorphism T869C (rs1800470; Leu10/Pro10; T29C, codon10) is significantly higher in the ISR group after coronary implantation of BMS among Chinese Han patients.…”

“…However, there are limited data assessing the impact of these variants on ISR. [32][33][34] Additionally, whether the genetic variations in TGF-β1 are associated with the risk of ISR after coronary implantation of bare metal stent (BMS) among Chinese Han patients has not been studied.…”

The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease

“…Growth factors such as bFGF, EGF, IGF-1, PDGFB, TGF-β1 and VEGF-A play important roles in VSMC and EC migration and proliferation, therefore playing important roles in the pathogenesis of atherosclerosis. Polymorphisms selected for this study was based on their functionality, which was understood as influencing the level of gene expression or given growth factor concentration (rs699947, rs4444903, rs180047) or on the association of a given polymorphism with other conditions (rs308395, rs699947, rs2285094) [15]. The growth factors that we analyzed in this paper are both acting on and secreted by ECs and VSMCs [16].…”

Correlation between high perfusion syndrome and stent restenosis after stent implantation

“…After hyperperfusion syndrome, cerebral artery hemodynamics change, inducing basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) expression, bFGF and PDGF may promote the division and proliferation of vascular endothelial cells, and induce migration proliferation of smooth muscle cells, ultimately lead to vascular intimal hyperplasia (16,17). Puffiness has creeping growth along the stent mesh, the stent neointimal coverage area increases, so that stent restenosis occurs.…”