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1.
Life Sci ; 232: 116547, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31176780

RESUMO

AIMS: This study aims to investigate the value of the expression of miR-208, miR-494, miR-499 and miR-1303 in the early diagnosis of acute myocardial infarction (AMI). MAIN METHODS: Patients were divided into two groups: AMI group (n = 41), and Stable angina pectoris (SAP) group (n = 32). Peripheral venous blood was sampled from these patients at the time of admission (T0), 6 h after onset (T6) and 12 h after onset (T12), while blood was sampled once from healthy subjects who underwent physical examination in the same time period (control group, n = 10). The expression of miR-208, miR-494, miR-499 and miR-1303 in serum were detected by real-time quantitative polymerase chain reaction (qRT-PCR), and differences in miRNA expression among these three groups of patients were analyzed. KEY FINDINGS: Serum miR-208, miR-494, miR-499 and miR-1303 expression levels at different time points were significantly higher in the AMI group than in the SAP group and control group. The differences among these groups were statistically significant (P < 0.05), while the difference between the SAP group and control group was not statistically significant (P > 0.05). Variation trend: The miRNA levels above began to increase at T0 in the AMI group, the peak levels of miR-208, miR-494 and miR-499 appeared before T12, and the peak level of miR-1303 appeared between T6 and T12, or after T12. SIGNIFICANCE: miR-208, miR-494, miR-499 and miR-1303 were not superior to hs-cTnI as myocardial markers in the diagnosis of early acute myocardial infarction.


Assuntos
MicroRNAs/genética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Idoso , Angina Estável/genética , Angina Estável/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma/genética , Troponina I/análise , Troponina I/sangue , Troponina T/análise , Troponina T/sangue
2.
Biosci Rep ; 38(5)2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30185439

RESUMO

There is increasing evidence that serum adipokine levels are associated with higher risks of cardiovascular diseases. As an important adipokine, fibroblast growth factor 21 (FGF21) has been demonstrated to be associated with atherosclerosis and coronary artery disease (CAD). However, circulating level of FGF21 in patients with angina pectoris has not yet been investigated. Circulating FGF21 level was examined in 197 patients with stable angina pectoris (SAP, n=66), unstable angina pectoris (UAP, n=76), and control subjects (n=55) along with clinical variables of cardiovascular risk factors. Serum FGF21 concentrations on admission were significantly increased more in patients with UAP than those with SAP (Ln-FGF21: 5.26 ± 0.87 compared with 4.85 ± 0.77, P<0.05) and control subjects (natural logarithm (Ln)-FGF21: 5.26 ± 0.87 compared with 4.54 ± 0.72, P<0.01). The correlation analysis revealed that serum FGF21 concentration was positively correlated with the levels of cardiac troponin I (cTnI) (r2 = 0.026, P=0.027) and creatine kinase-MB (CK-MB) (r2 = 0.023, P= 0.04). Furthermore, FGF21 level was identified as an independent factor associated with the risks of UAP (odds ratio (OR): 2.781; 95% CI: 1.476-5.239; P=0.002), after adjusting for gender, age, and body mass index (BMI). However, there were no correlations between serum FGF21 levels and the presence of SAP (OR: 1.248; 95% CI: 0.703-2.215; P=0.448). The present study indicates that FGF21 has a strong correlation and precise predictability for increased risks of UAP, that is independent of traditional risk factors of angina pectoris.


Assuntos
Angina Estável/genética , Angina Instável/genética , Doença da Artéria Coronariana/genética , Fatores de Crescimento de Fibroblastos/genética , Idoso , Angina Estável/sangue , Angina Estável/fisiopatologia , Angina Instável/sangue , Angina Instável/fisiopatologia , Aterosclerose/sangue , Aterosclerose/genética , Índice de Massa Corporal , Doença da Artéria Coronariana/fisiopatologia , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Troponina I/sangue
3.
Cell Mol Biol (Noisy-le-grand) ; 64(5): 1-6, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29729688

RESUMO

Cytokines, which typically regulate the immune responses, play a role in cardiovascular diseases such as coronary artery diseases (CAD) and ischemic heart diseases (IHD). The aims of this study were to evaluate serum levels of IL-6, IL-8, TGF-ß and TNF-α in patients with or without CAD, as well as stable angina, and to assess the effects of drug administration on the serum levels of these cytokines. Serum levels of the cytokines were analyzed in the three groups: patients with acute coronary syndrome, stable angina and participants with normal coronary arteries as controls. Cohort study of the patients showed that Nitrocontin was the only drug used in a significantly different pattern between the groups where it was used less frequently in patients with stable angina compared to the acute coronary syndrome or control groups. Serum levels of the evaluated cytokines were not different neither between the studied groups nor between the groups with variable Gensini scores. However, IL-8 in controls that were not engaged in regular exercise was higher than the controls performing regular exercise. In the stable angina group, TNF-α in non-smokers was higher than the smokers. It was revealed that serum levels of pro-inflammatory cytokines are not associated with atherosclerosis and stable angina in patients from the South-East of Iran. However, suppressed expression of TGF-ß, may increase the risk of CAD. Exercise can reduce the risk of CAD through downregulation of pro-inflammatory cytokines.


Assuntos
Angina Estável/sangue , Doença da Artéria Coronariana/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Fator de Crescimento Transformador beta/sangue , Fator de Necrose Tumoral alfa/sangue , Angina Estável/tratamento farmacológico , Angina Estável/genética , Angina Estável/patologia , Estudos de Casos e Controles , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Estudos Transversais , Exercício , Feminino , Expressão Gênica , Humanos , Interleucina-6/genética , Interleucina-8/genética , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Nitroglicerina/uso terapêutico , Fatores de Risco , Fumar/fisiopatologia , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/genética , Vasodilatadores/uso terapêutico
4.
Int Heart J ; 59(1): 43-50, 2018 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-29332918

RESUMO

We aimed to investigate the distinctive miRNA profiles in the plasma of elderly patients with unstable angina (UA) and stable angina (SA), and to find more effective markers of UA in elderly people. We compared miRNA expression levels in plasma samples from 10 elderly patients with UA and 10 elderly patients with SA by using microarray-based miRNA chip, and then performed validation with Real-time PCR. Mir-1202, mir-1207-5p, and mir-1225-5p showed a statistically significant down-regulation (P < 0.05), while mir-3162-3p showed an up-regulation (P < 0.05) during validation. Among all single miRNAs, miR-3162-3p showed the highest discriminatory power in the diagnosis of elderly patients with UA (AUC: 0.79, 95% CI: 0.675-0.905). The discriminatory power of a panel of three miRNAs (mir-3162-3p/mir-1225-5p/mir-1207-5p) was highest with an AUC of 0.91 (95% CI: 0.84-0.98), followed by mir-3162-3p/mir-1225-5p (AUC: 0.833, 95% CI: 0.732-0.934) and mir-3162-3p/mir-1207-5p (AUC: 0.817, 95% CI: 0.712-0.922). In conclusion, multi-miRNA panel could provide higher diagnostic value for the diagnosis of elderly patients with UA.


Assuntos
Angina Estável/genética , Angina Instável/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Fatores Etários , Idoso , Angina Estável/sangue , Angina Estável/diagnóstico , Angina Instável/sangue , Angina Instável/diagnóstico , Angiografia Coronária , Feminino , Seguimentos , Perfilação da Expressão Gênica/métodos , Marcadores Genéticos , Humanos , Masculino , MicroRNAs/biossíntese , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos
5.
Dis Markers ; 2017: 7909407, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29259350

RESUMO

Regulatory T cells (Tregs) play an essential role in acute coronary syndrome (ACS). However, there is debate about which Treg subsets are truly critical to ACS. Helios, a transcription factor, was recently reported to be a bona fide marker for natural Tregs or activated Tregs with a suppression function, but little is known about its role in ACS. We therefore examined Helios+ Tregs in patients with ACS, patients with stable angina, and control subjects. 73 patients with ACS, 30 patients with stable angina, and 48 control subjects were enrolled. The frequencies and estimated absolute numbers of different Treg subsets in peripheral blood were measured by flow cytometry. Plasma cytokine level was measured by ELISA. The mRNA expression of Foxp3 and Helios in purified CD4+ T cells was determined by RT-PCR. Helios+ Tregs was decreased significantly in patients with ACS. The frequency and estimated absolute numbers of CD4+Foxp3+Helios+ Tregs were negatively correlated with IL-6 and positively correlated with circulating level of TGF-beta1 and HDL-C. The mRNA expression of Foxp3 and Helios was decreased in CD4+ T cells from patients with ACS. In summary, Helios+ Tregs was downregulated in patients with ACS and may play a role in ACS.


Assuntos
Síndrome Coronariana Aguda/sangue , Angina Estável/sangue , Fator de Transcrição Ikaros/sangue , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/metabolismo , Angina Estável/genética , Angina Estável/metabolismo , Biomarcadores/sangue , Linfócitos T CD4-Positivos/metabolismo , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/metabolismo , Masculino , Pessoa de Meia-Idade
6.
J Biol Regul Homeost Agents ; 31(4): 1109-1113, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29254322

RESUMO

Cardiac surgery is accompanied by an important immune response that is poorly understood. This inflammatory response is caused by several stimuli: surgical trauma, cardiopulmonary bypass apparatus, aortic-cross clamping, reperfusion injury and hypothermia. The aim of the present study is to investigate the cytokine level profile involved in the inflammatory pathway of patients undergoing cardiac surgery. One hundred and two patients undergoing elective cardiac surgery utilizing cardiopulmonary bypass (CPB) apparatus were enrolled in the study. In the hematological and biochemical profiles investigated, we observed a significant increase of WBC and blood glucose concentration and a strong decrease of RBC, HB, HCT and PLT 24 h post-surgery compared to baseline and immediately after surgery groups. Furthermore, we found a modulation of cytokine levels mostly for IL-10 and an increase of IL-6, detected at 6 h post-surgery, IL-8 at 6 and 24 h, and TNFα only at 24 h post-surgery. In conclusion, these findings evidence a time course profile on cytokine levels and a balance between pro- and anti-inflammatory cytokine activation during and after cardiac surgery. In fact, IL-6 and IL-10, a pro- and an anti-inflammatory cytokine, respectively, increased immediately after surgery. The plasma level of TNF-α could be inhibited by the high concentration of IL-10 up to 6 h post-surgery. An IL-10 reduction at baseline level, after 24 h post-surgery, could explain a rise of TNF-α plasma concentration. On the other hand, considering the dual role of IL-6 on inflammation acting both as an activator of inflammatory cascade or an anti-inflammatory agent, the increased IL-6 levels 24 h after surgery could be related to the negative feedback action on TNFα activity.


Assuntos
Angina Estável/imunologia , Angina Instável/imunologia , Arritmias Cardíacas/imunologia , Ponte Cardiopulmonar , Infarto do Miocárdio/imunologia , Equilíbrio Th1-Th2/genética , Idoso , Angina Estável/sangue , Angina Estável/genética , Angina Estável/cirurgia , Angina Instável/sangue , Angina Instável/genética , Angina Instável/cirurgia , Arritmias Cardíacas/sangue , Arritmias Cardíacas/genética , Arritmias Cardíacas/cirurgia , Contagem de Células Sanguíneas , Glicemia/metabolismo , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-8/sangue , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Infarto do Miocárdio/cirurgia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
7.
Afr Health Sci ; 17(2): 474-480, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29062343

RESUMO

OBJECTIVE: This study aimed to explore the role of miR-126 in coronary artery disease (CAD) patients and the potential gene targets of miR-126 in atherosclerosis. METHODOLOGY: A total of 60 CAD patients and 25 healthy control subjects were recruited in this study. Among the 60 CAD patients, 18 cases were diagnosed of stable angina pectoris (SAP), 20 were diagnosed of unstable angina pectoris (UAP) and 22 were diagnosed of acute myocardial infarction (AMI). Plasma miR-126 levels from both groups of participants were analyzed by real-time quantitative PCR. ELISA was used to measure plasma level of placenta growth factor (PLGF). RESULTS: The results showed that the miR-126 expression was significantly down-regulated in the circulation of CAD patients compared with control subjects (P<0.01). Plasma PLGF level was significantly upregulated in patients with unstable angina pectoris and acute myocardial infarction (AMI) compared with controls (both P<0.01) the miR-126 expression in AMI was significantly associated with PLGF. CONCLUSION: miR-126 may serve as a novel biomarker for CAD.


Assuntos
Doença da Artéria Coronariana/genética , MicroRNAs/fisiologia , Angina Estável/genética , Angina Instável/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Fator de Crescimento Placentário/sangue , Reação em Cadeia da Polimerase em Tempo Real
8.
Circ Cardiovasc Genet ; 9(6): 541-547, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27872106

RESUMO

BACKGROUND: Serine and glycine interconversion and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-mediated 1-carbon transfer are the major sources of methyl groups for 1-carbon metabolism. Recently, plasma glycine and a common polymorphism in MTHFD1 have been associated with risk of acute myocardial infarction (AMI). It is, therefore, of interest to explore if these 2 pathways interact in relation to AMI. METHODS AND RESULTS: A total of 2571 participants in the WENBIT (Western Norway B Vitamin Intervention Trial) undergoing coronary angiography for stable angina pectoris were studied. Associations of plasma serine and glycine concentrations with risk of AMI across 2 common and functional MTHFD1 polymorphisms (rs2236225 and rs1076991) were explored in Cox regression models. During a median follow-up of 4.7 years, 212 patients (8.2%) experienced an AMI. In age- and sex-adjusted analyses, plasma glycine (P<0.01), but not serine (P=0.52), showed an overall association with AMI. However, interactions of MTHFD1 rs2236225 polymorphism with both plasma serine and glycine were observed (Pinteraction=0.03 for both). Low plasma serine and glycine were associated with an increased risk of AMI among patients carrying the rs2236225 minor A allele. Similarly, low plasma glycine showed stronger risk relationship with AMI in the rs1076991 CC genotype carriers but weaker associations in patients carrying the minor T allele (Pinteraction=0.02). CONCLUSIONS: Our results showed that 2 common and functional polymorphisms in the MTHFD1 gene modulate the risk associations of plasma serine and glycine with AMI. These findings emphasize the possible role of the MTHFD1 in regulating serine and glycine metabolism in relation to atherosclerotic complications. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00354081.


Assuntos
Angina Estável/genética , Glicina/sangue , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Antígenos de Histocompatibilidade Menor/genética , Infarto do Miocárdio/genética , Polimorfismo Genético , Serina/sangue , Idoso , Angina Estável/sangue , Angina Estável/diagnóstico por imagem , Angina Estável/enzimologia , Angiografia Coronária , Feminino , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/enzimologia , Noruega , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores de Tempo
9.
Mol Med Rep ; 14(6): 5350-5356, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27840920

RESUMO

The aim of the present study was to evaluate differences in the expression of complement system genes, and serum levels of CH50, C3 and C4 in peripheral blood mononuclear cells from patients with myocardial infarction (AMI), stable angina pectoris (SA) and controls. A total of 100 patients with AMI, 100 with SA and 100 clinical controls were recruited in the present study. In each group, 20 randomly selected individuals were examined using whole human genome microarray analysis to detect the expression of genes of the complement system. The serum levels of CH50, C3 and C4 were measured in all 300 subjects. In the patients with AMI, the expression levels of genes encoding C1qα, C1qß, C1qγ, C1r, Factor P, C5a (complement component), CR1, integrin αM, integrin αX, integrin ß2, C5aR, CRIg (complement receptors) and CD46, CD55 and CD59 (complement regulators) were significantly higher, compared with the respective genes in the SA patients and controls (P<0.05), whereas the mRNA levels of C1s, C7, C8ß and C9 were the lowest in this group (P<0.05). No statistically significant differences were found in the gene expression levels of complement components or regulators between the SA and control groups. The serum levels of CH50, C3 and C4 were significantly increased in the AMI and SA groups, compared with the controls. In the AMI and SA groups, the complement system was activated. However, the differential mRNA expression of complement components, receptors and regulators in the AMI group suggested the dysfunction of the C5b-9 complex. The depression of complement system immunity in the patients with AMI may be associated with the pathogenesis of AMI.


Assuntos
Proteínas do Sistema Complemento/imunologia , Infarto do Miocárdio/imunologia , Idoso , Angina Estável/sangue , Angina Estável/genética , Angina Estável/imunologia , Biomarcadores , Estudos de Casos e Controles , Proteínas do Sistema Complemento/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Receptores de Complemento/genética , Receptores de Complemento/metabolismo
10.
Cell Physiol Biochem ; 39(3): 837-46, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27497911

RESUMO

BACKGROUND: Coronary artery disease (CAD) is a major problem worldwide. As an endothelium-enriched microRNA (miRNA), miR-126 has been reported to serve as a potential biomarker of acute myocardial infarction. However, the relationship between miR-126 and the severity of CAD remains unknown. This study was designed to test whether circulating miR-126 levels are associated with the severity of CAD. METHODS: The present study enrolled 40 patients who had risk factors for CAD without angiographically significant CAD, and 110 patients presenting with stable angina pectoris, who were validated left main coronary artery disease (LMCA) and/or multi-vessel disease by coronary angiography. The expression levels of plasma miR-126-5p from all enrolled subjects were estimated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the relationships between plasma miR-126-5p levels, number of diseased vessels and the corresponding Synergy between PCI with Taxus and Cardiac surgery (SYNTAX) score were analyzed. RESULTS: The expression of circulating miR-126-5p was affected by some CAD risk factors including aging, dyslipidemia and DM. Furthermore, plasma miR-126-5p levels were significantly down-regulated in CAD patients with multi-vessel disease, higher SYNTAX score, rather than isolated LMCA and low SYNTAX score. CONCLUSION: Circulating miR-126-5p has emerged as a potential biomarker for complexity and severity of CAD in patients with stable angina pectoris.


Assuntos
Angina Estável/genética , Doença da Artéria Coronariana/genética , MicroRNAs/genética , Fatores Etários , Idoso , Angina Estável/complicações , Angina Estável/diagnóstico por imagem , Angina Estável/patologia , Biomarcadores/sangue , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Diabetes Mellitus/patologia , Dislipidemias/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Índice de Gravidade de Doença
11.
Nutr Metab Cardiovasc Dis ; 26(6): 495-501, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26803590

RESUMO

BACKGROUND: Methylenetetrahydrofolate dehydrogenase (MTHFD1) catalyzes three sequential reactions that metabolize derivatives of tetrahydrofolate (THF) in folate-dependent one-carbon metabolism. Impaired MTHFD1 flux has been linked to disturbed lipid metabolism and oxidative stress. However, limited information is available on its relation to the development of atherothrombotic cardiovascular disease. METHODS AND RESULTS: We explored the association between a MTHFD1 polymorphism (rs1076991 C > T) and acute myocardial infarction (AMI), and potential effect modifications by folic acid/B12 and/or vitamin B6 treatment in suspected stable angina pectoris patients (n = 2381) participating in the randomized Western Norway B Vitamin Intervention Trial (WENBIT). During the median follow-up of 4.9 years 204 participants (8.6%) suffered an AMI. After adjusting for established CVD risk factors, the MTHFD1 polymorphism was significantly associated with AMI (HR: 1.49; 95% CI, 1.23-1.81). A similar association was observed among patients allocated to treatment with vitamin B6 alone (HR: 1.53; 95% CI, 1.01-2.31), and an even stronger relationship was seen in patients treated with both vitamin B6 and folic acid/B12 (HR: 2.35; 95% CI, 1.55-3.57). However, no risk association between the MTHFD1 polymorphism and AMI was seen in patients treated with placebo (HR: 1.29; 95% CI, 0.86-1.93) or folic acid/B12 (1.17; 95% CI, 0.83-1.65). CONCLUSION: A common and functional MTHFD1 polymorphism is associated with increased risk of AMI, although the risk seems to be dependent on specific B vitamin treatment. Further studies are warranted to elucidate the possible mechanisms, also in order to explore potential effect modifications by nutritional factors.


Assuntos
Angina Estável/tratamento farmacológico , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Antígenos de Histocompatibilidade Menor/genética , Infarto do Miocárdio/prevenção & controle , Polimorfismo Genético , Complexo Vitamínico B/uso terapêutico , Idoso , Angina Estável/diagnóstico , Angina Estável/enzimologia , Angina Estável/genética , Feminino , Ácido Fólico/uso terapêutico , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Noruega , Fenótipo , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vitamina B 6/uso terapêutico
13.
Heart Vessels ; 31(1): 1-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25179298

RESUMO

Atherosclerosis is a disease characterized by inflammation in the arterial wall. Atherogenesis is dependent on the innate immune response involving activation of Toll-like receptors (TLRs) and the expression of inflammatory proteins, those may lead to acute coronary syndrome (ACS). We investigated the expression level of TLR-4 in ACS, as compared with TLR-2 and patients with stable angina. Fifty-eight consecutive patients who underwent primary percutaneous coronary intervention (PCI, n = 29) because of ACS and elective PCI (n = 29) because of stable angina using a filter-device distal protection device system were prospectively analyzed. mRNA levels of TLR-2 and TLR-4 in debris containing various inflammatory tissues entrapped in the filter device were altogether analyzed using real-time PCR. There were no significant differences in age, sex distribution, between stable angina and ACS groups. TLR-4 expression levels were higher in patients with ACS than in patients with stable angina. TLR-4 might play a more important role than TLR-2 in atherogenesis, especially in ACS.


Assuntos
Síndrome Coronariana Aguda/genética , Aterosclerose/genética , Placa Aterosclerótica/fisiopatologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Síndrome Coronariana Aguda/cirurgia , Idoso , Angina Estável/genética , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Placa Aterosclerótica/metabolismo , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Regulação para Cima
14.
Coron Artery Dis ; 27(2): 104-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26580301

RESUMO

BACKGROUND: Coronary artery disease (CAD) is a common complex disease caused by atherosclerosis. Autophagy is a cellular degradation process that delivers long-lived macromolecules and dysfunctional organelles into lysosomes for digestion. Autophagy regulates lipid and cholesterol metabolism. We have previously shown that expression of autophagic and lysosomal genes is altered in CAD patients. In this study, we investigated gene expression of a lysosomal hydrolase, acid α-glucosidase (GAA), in CAD patients and controls. METHODS: GAA gene expression was examined in large cohorts of CAD patients (n=248) and ethnically matched controls (n=208). GAA enzymatic activity, protein levels, and transcript levels were determined and compared between CAD patients and controls. RESULTS: GAA activities in CAD patients were significantly elevated (P<0.05) compared with controls. Consistently, GAA transcription levels were also significantly increased in CAD patients (P<0.01). Multivariate logistic regression analyses (GAA transcript level, hypertension, diabetes, and smoking) revealed that GAA transcript levels were strongly associated with CAD (odds ratio 5.93, 95% confidence interval 2.98-11.78, P=3.89×10(-7)). GAA protein levels were insignificantly increased in CAD patients (P>0.05), likely due to assay insensitivity. CONCLUSION: Compared with controls, GAA gene expression levels in CAD patients were significantly increased, suggesting that GAA may be involved in the CAD development.


Assuntos
Doença da Artéria Coronariana/genética , Isquemia Miocárdica/genética , RNA Mensageiro/metabolismo , alfa-Glucosidases/genética , Idoso , Angina Estável/genética , Angina Estável/metabolismo , Angina Instável/genética , Angina Instável/metabolismo , Western Blotting , Estudos de Casos e Controles , Estudos de Coortes , Doença da Artéria Coronariana/metabolismo , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Isquemia Miocárdica/metabolismo , Razão de Chances , Reação em Cadeia da Polimerase Via Transcriptase Reversa , alfa-Glucosidases/metabolismo
15.
Kardiologiia ; 56(3): 5-11, 2016 Mar.
Artigo em Russo | MEDLINE | ID: mdl-28294882

RESUMO

Great number of factors stimulating or inhibiting production of proteins in inflammatory process influence serum levels of markers of inflammation. A number of homozygous genotypes of inflammation, destruction, and angiogenesis genes have been found to be associated with basic clinical-laboratory indices of inflammation and atherosclerotic process. The revealed genetic markers can be used as complimentary markers of prognosis of the disease course.


Assuntos
Angina Estável/genética , Angina Estável/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Biomarcadores , Homozigoto , Humanos , Inflamação/genética , Masculino , Prognóstico
16.
J Biol Regul Homeost Agents ; 29(2): 437-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26122234

RESUMO

This study was conducted to investigate the effect of relative gene expression on plaque vulnerability in patients with either stable angina or acute coronary syndrome (ACS). A total of 30 patients with ACS, 28 patients with stable angina and 17 healthy volunteers were selected. High resolution ultrasound was used to detect carotid arterial intima-media thickness (IMT) and plaque score, Sandwich enzyme linked immunoassay to determine the change of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1. The three groups had no statistically significant difference in age, gender, total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. MMP-9, TIMP-1, MMP-9/TIMP-1 and IMT, total plaque score, soft plaque score and hard plaque score of patients’ acute coronary syndrome were obviously higher than those with stable angina and normal people. It was also found that MMP-9 was in a positive correlation with IMT, total and soft plaques score, TIMP-1 was positively correlated with IMT as was MMP-9/TIMP-1. Regardless of age, IMT was in a positive correlation with MMP-9, TIMP-1 and MMP-9/TIMP-1 in partial correlation analysis. All these findings suggest that ACS patients have remarkably higher MMP-9, 1TIMP-1, MMP- 9/TIMP-1, IMT, total plaque score, soft plaque score and hard plaque score compared to patients with stable angina pectoris and healthy subjects (P<0.05) and there are positive correlations between MMP- 9, TIMP-1, 1MMP-8/TIMP-1, total plaque and soft plaque score.


Assuntos
Síndrome Coronariana Aguda/genética , Angina Estável/genética , Estenose das Carótidas/patologia , Expressão Gênica , Metaloproteinase 8 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Placa Aterosclerótica/patologia , Inibidor Tecidual de Metaloproteinase-1/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/patologia , Idoso , Angina Estável/sangue , Angina Estável/patologia , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/patologia , Espessura Intima-Media Carotídea , Estenose das Carótidas/diagnóstico por imagem , Feminino , Humanos , Lipídeos/sangue , Masculino , Metaloproteinase 8 da Matriz/biossíntese , Metaloproteinase 8 da Matriz/genética , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Ruptura Espontânea , Índice de Gravidade de Doença , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Inibidor Tecidual de Metaloproteinase-1/genética
17.
BMC Complement Altern Med ; 15: 139, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25925670

RESUMO

BACKGROUND: Angina pectoris (Angina) is a medical condition related to myocardial ischemia. Although acupuncture has been widely accepted as a clinical approach for angina, there is no sufficient evidence of its effectiveness against this syndrome, and its mechanisms have not yet been well elucidated. We develop this protocol to confirm the clinical efficacy of electro-acupuncture on stable angina pectoris by needling on acupoint Neiguan (PC6). Furthermore, we employ high-throughput sequencing technology to investigate the gene expression profiling and determine involvement of histone modifications in the regulation of genes after electro-acupuncture treatment. METHODS/DESIGN: A randomized, controlled, double-blinded (assessor and patients) trial will be carried out. Sixty participants will be randomly assigned to two acupuncture treatment groups and one control group in a 1:1:1 ratio. Participants in acupuncture groups will receive 12 sessions of electro-acupuncture treatment across 4 weeks, followed by a 12-week randomization period. The acupuncture groups are divided into Neiguan (PC6) on Pericardium Meridian of Hand-jueyin or a non-acupoint. The primary clinical measure of effect is the frequency of angina attacks between these groups for four weeks after randomization. RNAs are extracted from peripheral neutrophils collected from all participants on day 0, day 30, and week 16, and are processed to RNA-Seq. We then investigate profiles of histone modifications by ChIP-Seq, for H3 Lysine 4 (H3K4me) and acetylation of H3 Lysine 27 (H3K27ac), in the presence or absence of acupuncture treatment. DISCUSSION: This study determines the efficacy and mechanisms of electro-acupuncture on stable angina pectoris. We focus on effectiveness of acupuncture on alleviating symptoms of myocardial ischemia and the gene regulation and the chromatin remodeling marks, including H3K4me1, H3K4me2, and H3K27ac, which could be key factors for regulating gene expressions caused by electro-acupuncture treatment at Neiguan. This is the first genome-wide study of electro-acupuncture treatment in angina patients, and will provide valuable information for future studies in the fields of acupuncture and its underlying mechanisms. Fourteen patients have been recruited since recruitment opened in November of 2012. This study is scheduled to end in November of 2014. TRIALS REGISTRATION: ChiCTR-TRC-12002668.


Assuntos
Angina Estável/terapia , Montagem e Desmontagem da Cromatina , Eletroacupuntura , Expressão Gênica , Histonas/metabolismo , Pontos de Acupuntura , Adulto , Idoso , Angina Pectoris , Angina Estável/genética , Protocolos Clínicos , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Lisina/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa
18.
Scand J Clin Lab Invest ; 75(5): 382-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25922869

RESUMO

BACKGROUND: In vitro and animal studies indicate that statins increase heme oxygenase-1 gene (HMOX1) expression, which then, presumably, increases plasma bilirubin concentration. However, clinical confirmation that statins concomitantly increase HMOX1 expression and plasma bilirubin concentration is lacking. We hypothesized that in patients with stable angina atorvastatin therapy (20 mg/day for 10 weeks) concomitantly increases total bilirubin concentration and HMOX1 expression, as assessed non-invasively by plasma analysis. METHODS: In 44 patients with stable angina plasma concentrations of total bilirubin, HMOX1 mRNA and HMOX1 protein were measured before and after the statin treatment, as well as plasma concentrations of oxidized low-density lipoprotein (OxLDL), malondialdehyde (MDA), monocyte chemoattractant protein (MCP-1) and C-reactive protein (CRP). RESULTS: Atorvastatin treatment increased total bilirubin concentration (median 6.95 µmol/L vs. 8.55, + 23.02%; p < 0.001), but did not change plasma HMOX1 mRNA and HMOX1 protein concentrations. Plasma concentrations of OxLDL (- 31.85%, p < 0.001), MCP-1 (- 16.20%, p = 0.020) and CRP (- 7.32%, p = 0.010) were decreased but MDA was not decreased (15.32%, p = 0.107). Within subjects, increment of plasma bilirubin concentration did not correlate with the changes in HMOX1 mRNA and protein concentrations, but correlated with low-density lipoprotein cholesterol decrement (r = - 0.374, p = 0.012). Bilirubin increment did not correlate with the changes in oxidative and inflammatory markers. CONCLUSION: Our prospective observational trial finally confirms that atorvastatin (20 mg/day for 10 weeks) increases plasma total bilirubin concentration. However, it seems that this effect is HMOX1-independent.


Assuntos
Angina Estável/sangue , Angina Estável/tratamento farmacológico , Atorvastatina/uso terapêutico , Bilirrubina/sangue , Heme Oxigenase-1/metabolismo , Angina Estável/enzimologia , Angina Estável/genética , Feminino , Regulação Enzimológica da Expressão Gênica , Heme Oxigenase-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteólise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
19.
J Cardiol ; 65(6): 494-500, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25156215

RESUMO

AIM: CYP2C19 polymorphism modulates platelet reactivity in coronary artery disease patients with stent implants. However, the impact of the CYP2C19 genotype on clopidogrel response and clinical outcome has not been fully understood to date. METHODS: We enrolled 518 consecutive patients with acute coronary syndrome (ACS) (n=214) and stable angina (SA) (n=304). All patients received stent implants followed by dual antiplatelet therapy of aspirin and clopidogrel. We determined CYP2C19 phenotype, measured platelet reactivity, and assessed the risk of cardiovascular events. RESULTS: During a median follow-up of 894 days, the rate of cardiovascular events was higher in patients of the ACS group than the SA group (ACS: 20.1%, SA: 12.5%, p=0.015). The mean platelet reactivity was significantly higher in the CYP2C19 loss-of-function allele carriers of the two groups (ACS, non-carriers: 3909±1836AUmin, carriers: 4854±1594AUmin, respectively, p<0.01; SA, 3606±1579AUmin, 4381±1373AUmin, ±SD, p<0.01). In the ACS group, cardiovascular events were higher in the loss-of-function allele carriers (24.6%) versus non-carriers (11.1%, p<0.05), but no such difference was noted in the SA group (carriers: 14.8%; non-carriers: 7.9%, p=0.078). Furthermore, landmark analysis from 30 days did not show differences in ACS group (carriers: 14.8%, non-carriers: 11.1%, p=0.315). Multivariate Cox proportional hazards analysis identified the presence of loss-of-function allele as an independent predictor of cardiovascular events (hazard ratio, 2.1, 95% CI, 1.194-3.587, p=0.010). CONCLUSIONS: The impact of CYP2C19 loss-of-function gene on clinical outcome is more powerful in early phase of ACS compared with SA.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Angina Estável/tratamento farmacológico , Citocromo P-450 CYP2C19/genética , Inibidores da Agregação de Plaquetas/uso terapêutico , Polimorfismo Genético , Síndrome Coronariana Aguda/genética , Idoso , Alelos , Angina Estável/genética , Aspirina/uso terapêutico , Plaquetas , Clopidogrel , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Resultado do Tratamento
20.
Eur J Prev Cardiol ; 22(6): 743-52, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24671904

RESUMO

AIM: To investigate whether plasma dimethylglycine was associated with and improved risk prediction of mortality among patients with coronary heart disease (CHD). METHODS: By Cox modelling, we explored the association between plasma dimethylglycine and mortality in two independent cohorts of patients with suspected stable angina pectoris (SAP) (n = 4156) and acute myocardial infarction (AMI) (n = 3733). We also assessed any improvement in risk prediction by adding plasma dimethylglycine to established CHD risk factors. RESULTS: Median follow-up time was 4.7 and 7.0 years among patients with SAP and AMI, respectively. Across both cohorts, elevated plasma dimethylglycine levels were linearly associated with increased risk of all-cause mortality (age and gender adjusted hazard ratios (95% confidence interval, CI) were 1.72 (1.21-2.46) and 1.76 (1.42-2.18) when comparing the fourth versus the first plasma dimethylglycine quartile in patients with SAP and AMI, respectively). There was a particularly strong risk association between plasma dimethylglycine and cardiovascular, as compared with non-cardiovascular, mortality (age and gender adjusted hazard ratios (95% CI) 1.94 (1.21-3.11) and 1.43 (0.83-2.47) among patients with SAP and 1.97 (1.50-2.59) and 1.44 (1.02-2.04) among patients with AMI, respectively). The relationship between dimethylglycine and all-cause and cardiovascular mortality was only slightly attenuated in analyses adjusted for established CHD risk factors. Plasma dimethylglycine also improved risk prediction for all-cause and cardiovascular mortality, and especially among patients with AMI. CONCLUSIONS: Elevated plasma dimethylglycine was associated with and improved risk prediction of mortality in patients with suspected or verified CHD. This relationship was stronger for death from cardiovascular, as compared with non-cardiovascular, causes.


Assuntos
Angina Estável/diagnóstico , Infarto do Miocárdio/diagnóstico , Sarcosina/análogos & derivados , Angina Estável/sangue , Angina Estável/genética , Angina Estável/mortalidade , Betaína-Homocisteína S-Metiltransferase/genética , Biomarcadores/sangue , Predisposição Genética para Doença , Humanos , Modelos Lineares , Modelos Logísticos , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Infarto do Miocárdio/mortalidade , Noruega , Fenótipo , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Sarcosina/sangue , Fatores de Tempo , Regulação para Cima
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