Angiotensinogen (AGT) represents a key component of the renin-angiotensin-aldosterone system (RAAS). Polymorphisms in the 3' untranslated region (3'UTR) of the AGT gene may alter miRNA binding and cause disbalance in the RAAS. Within this study, we evaluated the possible association of AGT +11525C/A (rs7079) with the clinical characteristics of patients with coronary artery diseases (CAD). Selective coronarography was performed in 652 consecutive CAD patients. Clinical characteristics of the patients, together with peripheral blood samples for DNA isolation, were collected. The genotyping of rs7079 polymorphism was performed with TaqMan® SNP Genotyping Assays. We observed that patients with the CC genotype were referred for coronarography at a younger age compared to those with the AA+CA genotypes (CC vs. AA+CA: 59.1 ± 9.64 vs. 60.91 ± 9.5 (years), p = 0.045). Moreover, according to the logistic regression model, patients with the CC genotype presented more often with restenosis than those with the CA genotype (p = 0.0081). In conclusion, CC homozygotes for rs7079 present with CAD symptoms at a younger age compared with those with the AA+CA genotype, and they are more prone to present with restenosis compared with heterozygotes.
(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM.
- MeSH
- diabetes mellitus 2. typu * komplikace genetika chirurgie MeSH
- interleukin-6 metabolismus MeSH
- kardiochirurgické výkony * MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- nemoci koronárních tepen * komplikace genetika chirurgie MeSH
- perikard metabolismus MeSH
- TNF-alfa genetika metabolismus MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.
- MeSH
- endoplazmatické retikulum genetika metabolismus MeSH
- exprese genu genetika MeSH
- kosterní svaly metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- mitochondrie genetika metabolismus MeSH
- myokard metabolismus MeSH
- nemoci koronárních tepen genetika patofyziologie MeSH
- perikard metabolismus MeSH
- podkožní tuk metabolismus MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- stres endoplazmatického retikula genetika fyziologie MeSH
- transkriptom genetika MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Adiponectin has several beneficial properties, namely, on the level of glucose metabolism, but paradoxically, its high concentrations were associated with increased mortality. We aimed to clarify the impact of high serum adiponectin on mortality and morbidity in patients with stable coronary artery heart disease (CAD). A total of 973 patients after myocardial infarction and/or coronary revascularization were followed in a prospective cohort study. All-cause and cardiovascular (CV) death, non-fatal cardiovascular events, and hospitalizations for heart failure (HF) were registered as outcomes. High serum adiponectin levels (≥8.58 ng/ml, i. e., above median) were independently associated with increased risk of 5-year all-cause, CV mortality or HF [with HRR 1.57 (95% CI: 1.07-2.30), 1.74 (95% CI: 1.08-2.81) or 1.94 (95% CI: 1.20-3.12), respectively] when adjusted just for conventional risk factors. However, its significance disappeared if brain natriuretic peptide (BNP) was included in a regression model. In line with this, we observed strong collinearity of adiponectin and BNP. Additionally, major adverse cardiovascular event (i. e., CV death, non-fatal myocardial infarction or stroke, coronary revascularization) incidence risk was not associated with high adiponectin. In conclusion, the observed inverse association between adiponectin concentrations and mortality risk seems to be attributable to concomitantly increased BNP, rather than high adiponectin being a causal factor.
- MeSH
- adiponektin krev MeSH
- biologické markery krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- morbidita MeSH
- následné studie MeSH
- nemoci koronárních tepen krev epidemiologie genetika mortalita MeSH
- prognóza MeSH
- prospektivní studie MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Coronary artery bypass graft (CABG) surgery is one of the most commonly performed operations worldwide. We compared genotype frequencies of three major cardiovascular disease (CVD)-associated genetic markers (ANRIL, FTO and 2q36.3 locus) between 753 patients who underwent CABG at the Institute for Clinical and Experimental Medicine (Prague, Czech Republic) and 2,559 controls from the Czech post-MONICA study. Subjects with at least one major A allele in the rs10757274 polymorphism (ANRIL) were more prevalent in patients after CABG than in the controls (81.7 % vs 72.7 %; OR [95 % CI] 1.67 [1.35-2.05]; P < 0.0001). In contrast, variants within the FTO gene (OR 0.87; 95 % CI, 0.70-1. 09 in a TT vs. GG comparison, P = 0.24) and 2q36.3 locus (OR 1.16; 95% CI, 0.98-1.37 in a +A vs. CC comparison, P = 0.08) were not significantly associated with CVD in our study. Variants were not associated with anthropometric, biochemical, or clinical characteristics within the patient group. Our study suggests that patients with CABG are more commonly carriers of some but not all CVD-associated alleles.
- MeSH
- gen pro FTO genetika MeSH
- genetické markery * MeSH
- genotyp MeSH
- koronární bypass * MeSH
- lidé MeSH
- nemoci koronárních tepen * genetika MeSH
- polymorfismus genetický MeSH
- RNA dlouhá nekódující genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
We sought to analyse plasma levels of peripheral blood microRNAs (miRs) as biomarkers of ST-segment-elevation myocardial infarction (STEMI) due to type-1 myocardial infarction as a model situation of vulnerable plaque (VP) rupture. Samples of 20 patients with STEMI were compared both with a group of patients without angina pectoris in whom coronary angiogram did not reveal coronary atherosclerotic disease (no coronary atherosclerosis-NCA) and a group of patients with stable angina pectoris and at least one significant coronary artery stenosis (stable coronary artery disease-SCAD). This study design allowed us to identify miRs deregulated in the setting of acute coronary artery occlusion due to VP rupture. Based on an initial large scale miR assay screening, we selected a total of 12 miRs (three study miRs and nine controls) that were tested in the study. Two of the study miRs (miR-331 and miR-151-3p) significantly distinguished STEMI patients from the control groups, while ROC analysis confirmed their suitability as biomarkers. Importantly, this was observed in patients presenting early with STEMI, even before the markers of myocardial necrosis (cardiac troponin I, miR-208 and miR-499) were elevated, which suggests that the origin of miR-331 and miR-151-3p might be in the VP. In conclusion, the study provides two novel biomarkers observed in STEMI, which may be associated with plaque rupture.
- MeSH
- akutní koronární syndrom genetika MeSH
- genetické markery genetika MeSH
- infarkt myokardu s elevacemi ST úseků genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- nemoci koronárních tepen genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Little is known about the role of adipokines in the pathogenesis of coronary artery disease in young patients. The aims of this study were to compare serum levels of adipokines and expression of adipokines in peripheral blood leukocytes in patients with premature coronary artery disease (CAD), metabolic syndrome and healthy individuals. DESIGN AND METHODS: Sixty-five patients with premature CAD (men 18-45years old and women 18-55years old) formed the study group. The control groups were 75 patients with metabolic syndrome and 50 healthy individuals. For each group, RNA expression in peripheral blood leukocytes was determined for 24 different adipokines and 11 adipokines were examined in serum. RESULTS: In individuals with CAD, serum visfatin levels were significantly higher than in metabolic syndrome and healthy controls (2.3 vs. 1.6 vs. 0.7µg/L, P<0.001) while both omentin-1 (92.9 vs. 587.0 vs. 552.3µg/L, P<0.001) and ZAG2 (45.5 vs. 72.5 vs. 77.1mg/L, P<0.001) levels were lower. The receiver operating curve (ROC) analysis for testing the validity of these adipokines in the diagnosis of CAD compared to control groups provided the following areas under the curve (AUC): omentin-1 AUC 0.97 (cut-off ≤222µg/L), ZAG2 AUC 0.89 (cut-off ≤51.7mg/L) and visfatin AUC 0.74 (cut-off ≥1.0µg/L) (P<0.001 in all cases). Visfatin and omentin-1 serum levels did not differ between the acute phase of myocardial infarction and the chronic phase of CAD. In patients with CAD, we found no significant relation between mRNA expression and adipokine concentration. CONCLUSION: Serum omentin-1, visfatin and ZAG2 could serve as biomarkers of premature CAD in young apparently healthy people.
- MeSH
- adipokiny krev genetika metabolismus MeSH
- cytokiny krev genetika MeSH
- dospělí MeSH
- GPI-vázané proteiny krev genetika MeSH
- infarkt myokardu krev genetika MeSH
- kohortové studie MeSH
- lektiny krev genetika MeSH
- leukocyty metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA krev MeSH
- metabolický syndrom krev genetika MeSH
- mladiství MeSH
- nemoci koronárních tepen krev genetika MeSH
- nikotinamidfosforibosyltransferasa krev genetika MeSH
- podkožní tuk metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
- MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- infarkt myokardu genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 9 * MeSH
- nemoci koronárních tepen genetika patologie MeSH
- odds ratio MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: The study was designed to test the possible association between either polymorphisms of the matrix metalloproteinase-9 (MMP-9) gene (rs17576, rs3918242) or the MMP-3 5A/6A gene polymorphism (rs3025058) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The second aim of the study was to demonstrate an association between either the rs17576, rs3918242 or rs3025058 and subclinical markers of coronary artery disease in the same subset of patients with T2DM. PATIENTS AND METHODS: A total of 595 subjects with T2DM and 200 subjects without T2DM (control group) were enrolled in the prospective study. Subclinical markers of carotid atherosclerosis were assessed ultrasonographically. Additionally, in a subset of subjects with T2DM a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of all three polymorphisms (rs17576, rs3918242, rs3025058) was performed with real-time PCR systems. RESULTS: The comparison of atherosclerosis parameters was performed with regard to different genotypes of MMP-9 rs17576, rs3918242, and MMP-3 rs3025058 polymorphisms upon enrolment and during follow-up. In our study, we found an association between the MMP-3 rs3025058 and CIMT at the time of recruitment. Multiple linear regression analysis revealed the association of either the A- allele or the A- genotypes of the rs3025058 (MMP-3) with carotid intima media thickness (CIMT) progression in a 3.8-year follow-up. We demonstrated the effect of the rs3025058 on subclinical markers of coronary atherosclerosis (coronary calcium score, number of coronary arteries with more than 50 % stenosis, and presence of at least one vessel with more than 50 % stenosis). CONCLUSIONS: We found an association between the MMP-3 rs3025058 and subclinical markers of carotid (CIMT) and coronary atherosclerosis at the time of recruitment. Moreover, we demonstrated the effect of the MMP-3 rs3025058 on CIMT progression in the 3.8-year follow-up in patients with T2DM.
- MeSH
- asymptomatické nemoci MeSH
- časové faktory MeSH
- diabetes mellitus 2. typu diagnóza enzymologie genetika MeSH
- fenotyp MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- intimomediální šíře tepenné stěny MeSH
- jednonukleotidový polymorfismus * MeSH
- koronární angiografie MeSH
- koronární stenóza diagnostické zobrazování enzymologie genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- matrixová metaloproteinasa 3 genetika MeSH
- matrixová metaloproteinasa 9 genetika MeSH
- multivariační analýza MeSH
- nemoci arterie carotis diagnostické zobrazování enzymologie genetika MeSH
- nemoci koronárních tepen diagnostické zobrazování enzymologie genetika MeSH
- prognóza MeSH
- prospektivní studie MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- rozdělení chí kvadrát MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIM: The purpose of this study is to determine the association between eotaxin 426 C/T, -384 A/G, 67 G/A, eNOS -786 T/C, 4 a/b, and MMP-13 rs640198 G/T and prognosis of patients with known CAD. METHODS: From total of 1161 patients referred to coronary angiography, 532 patients with angiographically confirmed CAD were selected. Their long-term outcome was followed up using hospital database. Subsequent events were assessed in this study: death or combined endpoint-myocardial infarction, unstable angina pectoris, revascularization, heart failure hospitalization, and cardioverter-defibrillator implantation. RESULTS: The multivariate Cox regression model identified age, smoking, and 3-vessel disease as significant predictors of all-cause death. Further analysis showed that eotaxin 67 G/A (GA + AA versus GG) and eotaxin -384 A/G (GG versus GA + AA) were significant independent prognostic factors when added into the model: HR (95% CI) 2.81 (1.35-5.85), p = 0.006; HR (95% CI) 2.63 (1.19-5.83), p = 0.017; eotaxin -384 A/G was significantly associated with the event-free survival, but it did not provide the prognostic information above the effect of two- or three-vessel disease. CONCLUSION: The A allele in eotaxin 67 G/A polymorphism is associated with worse survival in CAD patients.
- MeSH
- chemokin CCL11 genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 13 genetika MeSH
- nemoci koronárních tepen diagnóza genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- synthasa oxidu dusnatého, typ III genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
