| Object:The aim of this study was to investigate the relationship among plasma level of platelet-derived growth factor (PDGF)-BB, mRNA expression of PDGF-B and platelet-derived growth factor receptor (PDGFR)-β, and the restenosis in a balloon injury model of rabbit carotid arteries. In order to investigated the effects of Imatinib mesilate (Imatinib) on neointimal hyperplasia. We also studied whether PDGF-B gene single nucleotide polymorphism (SNP) can predict human clinical restenosis after stent placement, and the relation between PDGF-B gene SNPs and PDGF-BB plasma level.Method:Thirty adult Newzealand rabbits were divided into three groups, group A, B and C randomly. They received balloon injury on their right carotid arteries and were daily administered with0.25or50mg/kg of Imatinib for14days. The carotid arteries were excised for HE-staining and mRNA extraction. Quantitative Real-Time Reverse Transcription-PCR (RT-PCR) Analysis was used to assay PDGF-B and PDGFR-β mRNA expression.138patients who had underwent coronary artery stenting for more than half year were enrolled, and they were divied into ISR and NISR group according to the angiographic diagnosis of in-stent restenosis (ISR). Plasma level of PDGF-BB was measured by enzyme-linked immunosorbent assay (ELISA). DNA was isolated from leukocytes. Two SNPs concerning the PDGF-B gene (+286A/G,+1135A/C) were determined by Taqman Quantitative Real-Time PCR with TaqMan MGB (Minor Groove Binder) probe.Results:Part1:①Intimal hyperplasia and arterial stenosis following balloon injury were seen in three groups. There was a downtrend of thickness of neointima, A>B>C.②mRNA expression of PDGF-B increased significently in group A than that in group B and C (P<0.01). While, the mRNA expression of PDGFR-β increased significently in group C than that in group A and B (P<0.05).③Plasma level of PDGF-BB increased in each group after balloon injury than the baseline (P<0.01). The highest plasma level was in group A. There was no difference between group B and C.④There was positive correlation between mRNA expression of PDGF-B and plasma level of PDGF-BB (r=0.776, P<0.01). PDGFR-β mRNA expression has no relationship with plasma level of PDGF-BB. Part2:①The percentage of male, white blood cell count (WBC). and plasma level of PDGF-BB in ISR group were higher than that in NISR group (P<0.05). The ejection fraction (EF) was lower in ISR group (P<0.05).②The allele frequency of+286A/G were0.355and0.645respectively. There were no differences of genotype distributions beween ISR group and NISR group (P>0.05), though the frequency of A allele in ISR group was much higher than in NISR group (P<0.05).③Plasma level of PDGF-BB was significantly high in patients with AA genotype compared with AG and GG genotypes when all patients were analysed (P<0.01), while this difference was much higher between ISR group and NISR group.④The allele frequency of+1135A/C were0.957and0.043respectively.⑤There were no differences of genotype distributions beween ISR group and NISR group (P<0.05), genotype CC hadn’t been found.⑥There were no differences of plasma level of PDGF-BB between AA and AC genotype.⑦Multivariable logistic regression was used to analyze the relation between clinical characteristics. PDGF-B gene SNPs and occurrence of restenosis. Risk factors of ISR were plasma level of PDGF-BB (OR1.166,95.0%C.I.1.025～1.325), WBC (OR1.322,95.0%C.I.1.020～1.714). EF (OR0.935.95.0%C.I.0.887～0.986).Conclution:Vascular injury can cause intimal hyperplasia. arterial stenosis and PDGF-B mRNA expression increased. Imatinib mesilate has an effection of inhibition on the formation of intimal hyperplasia. PDGF-B gene+286,+1135SNPs were not associated with ISR. but plasma level of PDGF-BB was significiently higher in ISR group and homozygous AA genotype carriers. We hypothesized that+286A allele may affect the occurrence of ISR through increasing the plasma level of PDGF-BB. |
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