angiotensinogen and Coronary-Restenosis

We studied the relation between renin-angiotensin system (RAS) related gene polymorphisms, such as angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M253T and angiotensin II type 1 receptor (AT1R) A1166C, and the effect of quinapril, an ACE inhibitor with high tissue-binding affinity, on preventing restenosis after percutaneous coronary intervention (PCI). A total of 253 patients successfully treated for coronary artery disease were randomly assigned to quinapril or control. Of the 215 patients who completed the follow-up, we determined gene polymorphisms in 204 patients with 241 lesions who provided blood samples for genotype determination. In the control, the ACE D homozygotes showed a smaller minimal lumen diameter (MLD) at follow-up (P=0.063). The other two genotypes of AGT and AT1R did not affect restenosis after PCI. According to quinapril treatment, the AGT T homozygotes significantly showed a beneficial effect of quinapril on MLD (P=0.013) and late lumen loss (P=0.013). The ACE I homozygotes also exhibited beneficial effects of quinapril on larger MLD (P=0.065). The AT1R genotype did not influence the quinapril effect. In conclusion, the AGT T homozygotes might benefit from effects of quinapril on preventing restenosis after PCI.

Topics: Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Coronary Disease; Coronary Restenosis; Female; Gene Frequency; Genotype; Humans; Isoquinolines; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Quinapril; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Tetrahydroisoquinolines

This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.

Topics: Aged; Angiotensinogen; Coronary Artery Disease; Coronary Restenosis; Cytochrome P-450 CYP11B2; Drug-Eluting Stents; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Real-Time Polymerase Chain Reaction; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin; Renin-Angiotensin System

Percutaneous coronary intervention, despite being effective for coronary revascularization, causes in-stent restenosis due to neointimal hyperplasia in a large number of patients. The renin-angiotensin system is involved in neointimal hyperplasia. This study sought to evaluate seven gene polymorphisms of key renin-angiotensin system components, including angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1a receptors, and their associations with in-stent restenosis in patients with coronary artery disease following coronary stenting.. Three hundred and fifty-two patients undergoing coronary drug-eluting stent implantation were recruited. Seventy-five patients (21.3%) were diagnosed as restenosis by angiography. Genotyping for angiotensin-converting enzyme insertion/deletion demonstrated a significant association of angiotensin-converting enzyme DD genotype with the occurrence of restenosis. Direct DNA sequencing revealed no association of angiotensinogen (M235T, G217A, G152A, G-6A, and A-20C) or angiotensin II type I receptor A1166C polymorphisms with in-stent restenosis. However, angiotensin II type 1a A1166C polymorphism was significantly associated with increased susceptibility to restenosis in a subgroup of patients aged more than 60 years.. Thus, our study suggests that genetic polymorphisms of angiotensin-converting enzyme insertion/deletion are associated with in-stent restenosis in coronary artery disease patients following coronary stenting.

Topics: Aged; Angiotensinogen; Base Sequence; Coronary Restenosis; Female; Gene Frequency; Genetic Association Studies; Humans; Linkage Disequilibrium; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Stents

The renin-angiotensin-aldosterone system may influence in-stent restenosis (ISR) via angiotensin II, which stimulates the production of growth factors for smooth muscle cells. The aim of this work is to assess the influence of the rs1799752 polymorphism of the angiotensin-converting enzyme (ACE) gene and the rs699 polymorphism of the angiotensinogen (AGT) gene on the ISR in Polish patients with stable coronary artery disease (SCAD) who underwent stent implantation.. Two hundred and sixty-five patients with SCAD were included in the study. All patients underwent stent implantation upon admission to the hospital and had subsequent coronary angiography performed. The patients were divided into two groups - those with significant ISR (n=53) and those without ISR (n=212). The ACE polymorphism was assessed using the classical PCR method and the AGT polymorphism was determined using the TaqMan method for SNP genotyping.. No difference in the frequency of angiographically significant ISR occurrence associated with the different ACE and AGT gene polymorphisms was observed. In a multivariable analysis, after correction for clinical variables, the relationship between the ACE and AGT genotypes within the scope of the analyzed polymorphisms and the process of restenosis was not found using a dominant, recessive and log-additive model. Late lumen loss was also independent of the genotypes of the polymorphisms before and after correction with angiographic variables.. The rs1799752 polymorphism and the rs699 polymorphism had no relationship with the occurrence of angiographically significant ISR and late lumen loss in a group of Polish patients who underwent metal stent implantation.

Topics: Aged; Angiotensinogen; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Poland; Polymorphism, Single Nucleotide; Stents

The aim of the present study was to evaluate the role of AGT and REN gene polymorphisms as susceptibility markers for coronary artery disease (CAD) and/or restenosis after coronary stent placement in a group of Mexican patients. Five polymorphisms of the AGT (rs699, rs4762, rs5051, rs5049, rs5046) and two of the REN (rs5707, rs5705) genes were analyzed by 5' exonuclease TaqMan genotyping assays in 240 patients with CAD who underwent coronary artery stenting (76 with restenosis and 164 without restenosis). A group of 610 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. The results showed that the distribution of AGT and REN polymorphisms were similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant, heterozygous and additive models, the REN A4280C (rs5705) polymorphism was associated with increased risk of CAD (OR=1.76, PCo-dom=0.006, OR=1.81, PDom=0.001, OR=1.75, PHet=0.003 and OR=1.59, PAdd=0.003, respectively). All models were adjusted for age, gender, diabetes, dyslipidemia, hypertension and smoking habit. The TC haplotype of the REN gene was associated with increased risk of CAD (OR=1.53, P=0.014). The data suggest that the REN C4280A (rs5705) polymorphism plays an important role in the risk of developing CAD with the highest risk for C allele, but do not support its role as a risk factor for developing restenosis after coronary stenting.

Topics: Aged; Alleles; Angiotensinogen; Case-Control Studies; Computational Biology; Coronary Artery Disease; Coronary Restenosis; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Genotyping Techniques; Haplotypes; Heterozygote; Humans; Linkage Disequilibrium; Logistic Models; Male; Mexico; Middle Aged; Polymorphism, Single Nucleotide; Renin; Risk Factors; Stents

Although great progress has been made in reducing renarrowing of the lumen after stenting of coronary arteries, a considerable number of patients develop recurrent in-stent stenosis. Several studies suggest that neointimal proliferation is the crucial pathophysiological process underlying restenosis after stenting. The renin-angiotensin-aldosterone system (RAS) has been implicated in the development of neointimal hyperplasia. We tested the hypothesis that polymorphisms of the RAS genes are associated with recurrent in-stent restenosis (ISR). Coronary stent implantation was performed in 272 patients with clinical symptoms or objective signs of ischemia. At follow-up angiography 6 months after stenting, 81 patients (29.8%) revealed in-stent restenosis. These patients underwent balloon angioplasty and were scheduled for a further 6 months of follow up. One year after initial stenting of the coronary artery, 39 patients displayed no significant angiographic ISR, whereas 42 patients developed recurrent in-stent restenosis (RISR). The survey of specific functional polymorphisms of the RAS, namely the angiotensin-I converting enzyme (ACE) D/I, the angiotensinogen (AGT) T174M and M235T, and A1166C of the angiotensin-II receptor 1 (AGTR1), revealed that the incidence RISR in the high-risk cohort was not associated with any of the polymorphisms examined in this study.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Angiotensinogen; Cell Proliferation; Coronary Angiography; Coronary Restenosis; Diabetes Mellitus; Female; Gene Deletion; Human Growth Hormone; Humans; Male; Middle Aged; Myocardial Ischemia; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Recurrence; Renin-Angiotensin System; Stents

The renin-angiotensin system (RAS) is thought to play a major role in the pathophysiology of de-novo restenotic lesions and in-stent restenosis after percutaneous coronary intervention (PCI). Heme oxygenase-1 (HO-1), is thought to beneficially influence these processes. We examined the effect of pharmacologic as well as genetic RAS interactions on restenosis in a large population of consecutive patients undergoing PCI, and evaluated possible gene-gene interactions in both systems.. The GENDER project is a multicenter prospective follow-up study, including 3146 patients after successful PCI. Genotyping in these patients was performed for the ACE gene insertion/deletion, the angiotensinogen 235Met/Thr, T174M and A(-6)G, the angiotensin-II type 1 receptor (AT1R) 1166A/C and T810A, the angiotensin-II type 2 receptor (AT2R) 1675G/A and 3123A polymorphisms and the length polymorphism in the HO-1 promoter region.. A total of 3104 patients were followed for 10 months. In 2975 patients at least one of the nine genotypes could be determined. The AT1R 1166 CC genotype showed a significant association with TVR; the other polymorphisms did not. RAS-inhibitory drugs were not associated with the incidence of TVR, nor did they interact with any of the investigated polymorphisms. Patients with the ACE I/I polymorphism showed a trend towards a better outcome if they had a short number of repeats in the HO-1 promoter. This relationship was inversely present in carriers of the ACE D/D polymorphism.. We could only establish a role for the AT1R 1166A/C polymorphism in restenosis after PCI. However, significant gene-gene interaction was suggested for the ACE gene and the HO-1 promotor. The RAS and HO-1 relation in restenosis merits further investigation.

Topics: Alleles; Angioplasty, Balloon, Coronary; Angiotensinogen; Coronary Disease; Coronary Restenosis; Follow-Up Studies; Heme Oxygenase-1; Humans; Multicenter Studies as Topic; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Promoter Regions, Genetic; Prospective Studies; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Time Factors; Treatment Outcome

Intimal proliferation is a main cause of in-stent restenosis. Over-excretion of angiotensin I converting enzyme (ACE) and aldosterone is reported to stimulate intimal hyperplasia and the genetic effect of these molecules may alter the process of in-stent restenosis. We hypothesized that the genetic polymorphisms that alter the expression of genes such as ACE I/D, CYP11B2-344C/T, and AGT M235T can affect in-stent restenosis. We analyzed the angiographic and clinical data of 238 patients (272 stents) who underwent coronary stenting and follow-up angiography, and analyzed the genotypes of ACE I/D, CYP11B2-344T/C, and AGT M235T. There was no significant difference in age, sex, or lipid profiles between the patent and restenosis groups. Diabetes mellitus was more frequent in the binary restenosis group. Quantitative computer-assisted angiographic (QCA) analysis revealed that the risk of in-stent restenosis increased with lesion length and was inversely proportional to post- stenting minimal luminal diameter (MLD) and reference diameter. There was no difference in the frequency of binary restenosis between genotypes in each of the three genes. However, follow-up MLD was significantly smaller in the ACE DD genotype than in the ACE II or ID genotypes. Defining restenosis as MLD < 2 mm, the restenosis rate was significantly higher in the ACE DD genotype than in the ACE II or ID genotypes. There was no significant synergistic effect between the three gene polymorphisms. In conclusion, while the ACE I/D polymorphism promoted the progress of in-stent restenosis and was of clinical significance, the other potential variables examined did not correlate with in-stent restenosis.

Topics: Adult; Aged; Angiotensinogen; Coronary Restenosis; Cytochrome P-450 CYP11B2; Female; Genotype; Humans; Logistic Models; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Risk Factors; Stents