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1.
Article in Chinese | WPRIM | ID: wpr-878952

ABSTRACT

To explore the action mechanism of Xuefu Zhuyu Decoction in treating myocardial infarction based on network pharmaco-logy and molecular docking. Active components and corresponding targets of Xuefu Zhuyu Decoction were obtained through Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and related targets of myocardial infarction were obtained through GeneCards, DisGeNET, and OMIM databases. Then the intersection targets were obtained by integrating the drug targets and disease targets. The "active component-target" network was constructed by Cytoscape software, and protein-protein interaction(PPI) network was drawn using STRING platform. Protein cluster analysis was carried out using MCODE. GO enrichment analysis and KEGG pathway analysis were carried out using DAVID database and ClueGO, and molecular docking was carried out using Autodock Vina and Pymol. Finally, 226 active components of Xuefu Zhuyu Decoction were obtained, 257 corresponding targets, 1 340 targets of myocardial infarction, and 109 drug and disease intersection targets were obtained. From GO enrichment analysis, 208 biological process terms, 38 molecular function terms, and 33 cellular component terms were obtained. From KEGG pathway analysis, NF-κB signaling pathway, IL-17 signaling pathway, HIF-1 signaling pathway, and other related pathways were obtained. The molecular docking results showed that the main active components(quercetin, kaempferol, β-sitosterol, luteolin, stigmasterol and baicalein) of Xuefu Zhuyu Decoction in the treatment of myocardial infarction had good binding properties with the core proteins IL6, ALB, VEGFA, TNF, MAPK3 and CASP3. The results suggested that Xuefu Zhuyu Decoction may play a role in the treatment of myocardial infarction by reducing the inflammatory response, reducing oxidative stress, inhibiting cell apoptosis, and promoting angiogenesis.


Subject(s)
Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Myocardial Infarction/genetics
2.
Article in Chinese | WPRIM | ID: wpr-879530

ABSTRACT

OBJECTIVE@#To assess the association of CYP2C19 and CYP3A5 gene polymorphisms with the risk of myocardial infarction.@*METHODS@#Five hundred patients with myocardial infarction and 500 healthy controls were randomly selected. Fluorescent PCR and Sanger sequencing were used to detect the CYP2C19 and CYP3A5 gene polymorphisms. Logistic regression was used to analyze the correlation between the polymorphisms and myocardial infarction. Quanto software was used to evaluate the statistical power.@*RESULTS@#The two groups had significant difference in the frequency of AG, GG genotypes and A allele of the CYP2C19 gene rs4986893 locus and the AA, AG, GG genotypes and G allele of the CYP3A5 gene rs776746 locus ( P<0.05), but not in the frequency of genotypes and alleles of CYP2C19 gene rs4244285 and rs12248560 loci, and the AA genotype of the rs4986893 locus. After correction for age, gender, and body mass index, Logistic regression indicated that the AG genotype and A allele of the CYP2C19 gene rs4986893 locus, and the GG genotype and G allele of CYP3A5 gene rs776746 locus are associated with susceptibility of myocardial infarction, while rs4986893 GG genotype and AA and AG genotypes of rs776746 may confer a protective effect. Based on the sample size and allele frequency, analysis with Quanto software suggested that the result of this study has a statistical power of 99%.@*CONCLUSION@#CYP2C19 and CYP3A5 gene polymorphisms may increase the risk for myocardial infarction.


Subject(s)
Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP3A/genetics , Gene Frequency , Genotype , Humans , Myocardial Infarction/genetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide
3.
Arq. bras. cardiol ; 114(2): 234-242, Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1088869

ABSTRACT

Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.


Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.


Subject(s)
Animals , Male , DNA Damage/genetics , Heart Failure/genetics , Reference Values , Rats, Wistar , Oxidative Stress , Muscle, Skeletal/pathology , Comet Assay , Single-Cell Analysis , Heart Failure/pathology , Heart Ventricles/pathology , Hemodynamics , Liver/pathology , Lung/pathology , Myocardial Infarction/genetics , Myocardial Infarction/pathology
4.
Clinics ; 74: e1237, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039571

ABSTRACT

OBJECTIVES: To explore the clinical significance and correlation of microRNA-21 (miR-21) and the neutrophil-lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI). METHODS: The observation group contained 184 patients, while the control group contained 150 patients. The expression of miR-21 in the serum of each group was detected by qRT-PCR. RESULTS: A total of 184 patients and their family members were followed-up for 30 days, among which 35 patients died and 149 patients survived, resulting in a survival rate of 80.97%. According to univariate analysis, there were significant differences in age, cardiac troponin (cTn), heart rate, Killip grade, percutaneous coronary intervention (PCI) operation rate, miR-21 and NLR. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) values of miR-21 and NLR for the diagnosis of AMI were 0.909 and 0.868, respectively, and the area under the combined detection curve was 0.960. In the Kaplan-Meier survival analysis, the survival of patients with high miR-21 expression and NLR was significantly higher than that of patients with low miR-21 expression and NLR (p=0.027; p=0.001). The correlation showed that miR-21 expression in serum was positively correlated with the NLR in the observation group (r=0.528, p<0.05). cTn, heart rate, Killip classification, PCI operation rate, miR-21, NLR are independent risk factors for AMI. CONCLUSION: miR-21 and NLR play a role in the diagnosis of AMI and can be used as predictors for the survival of AMI.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Lymphocyte Count , MicroRNAs/genetics , Myocardial Infarction/diagnosis , Myocardial Infarction/blood , Neutrophils , Biomarkers , Case-Control Studies , Risk Factors , ROC Curve , Sensitivity and Specificity , Kaplan-Meier Estimate , Real-Time Polymerase Chain Reaction , Myocardial Infarction/genetics
5.
Braz. j. med. biol. res ; 51(11): e7660, 2018. tab, graf
Article in English | LILACS | ID: biblio-951727

ABSTRACT

Lactate modulates the expression of lactate oxidation complex (LOC)-related genes and cardiac blood flow under physiological conditions, but its modulatory role remains to be elucidated regarding pathological cardiac stress. The present study evaluated the effect of lactate on LOC-related genes expression and hemodynamics of hearts submitted to myocardial infarction (MI). Four weeks after MI or sham operation, isolated hearts of male Wistar rats were perfused for 60 min with Na+-lactate (20 mM). As expected, MI reduced cardiac contractility and relaxation with no changes in perfusion. The impaired cardiac hemodynamics were associated with increased reactive oxygen species (ROS) levels (Sham: 19.3±0.5 vs MI: 23.8±0.3 µM), NADPH oxidase (NOX) activity (Sham: 42.2±1.3 vs MI: 60.5±1.5 nmol·h−1·mg−1) and monocarboxylate transporter 1 (mct1) mRNA levels (Sham: 1.0±0.06 vs MI: 1.7±0.2 a.u.), but no changes in superoxide dismutase (SOD), catalase, NADH oxidase (NADox), and xanthine oxidase activities. Lactate perfusion in MI hearts had no additional effect on ROS levels, NADox, and NOX activity, however, it partially reduced mct1 mRNA expression (MI-Lactate 1.3±0.08 a.u.). Interestingly, lactate significantly decreased SOD (MI-Lactate: 54.5±4.2 µmol·mg−1·min−1) and catalase (MI: 1.1±0.1 nmol·mg−1·min−1) activities in MI. Collectively, our data suggest that under pathological stress, lactate lacks its ability to modulate the expression of cardiac LOC-related genes and the perfused pressure in hearts submitted to chronic MI. Together, these data contribute to elucidate the mechanisms involved in the pathogenesis of heart failure induced by MI.


Subject(s)
Animals , Male , Lactic Acid/metabolism , Lactic Acid/pharmacology , Heart Ventricles/drug effects , Heart Ventricles/metabolism , Myocardial Infarction/genetics , Myocardial Infarction/metabolism , Perfusion , Time Factors , Catalase/analysis , Gene Expression , Rats, Wistar , Lactic Acid/analysis , Multienzyme Complexes/analysis , NADH, NADPH Oxidoreductases/analysis
6.
Clinics ; 71(12): 725-732, Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-840021

ABSTRACT

OBJECTIVES: The number of deaths from vascular diseases is incredibly high worldwide, and reliable markers for major events are still needed. The current cross-sectional study investigated the association of Klotho haplotypes and Klotho serum levels with classic risk factors and a clinical history of vascular events. METHODS: Clinical, anthropometric, biochemical and nutritional assessments were conducted with 168 older adults, complemented by genotyping (rs9536314 and rs9527025) and the detection of serum Klotho (ELISA). RESULTS: Klotho levels and haplotypes did not associate with most classic risk factors for vascular events, including markers such as C-reactive protein and homocysteine. A positive association was only found between Klotho levels and the previous occurrence of a myocardial infarction by both correlational (p=0.006) and variance analyses (p<0.001), and these associations were independent of the context. CONCLUSION: Our results suggest that serum Klotho is higher in individuals with a clinical history of myocardial infarction but not with a history of coronary artery disease or stroke. None of the Klotho haplotypes were associated with the variables investigated herein.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Glucuronidase/genetics , Glucuronidase/blood , Myocardial Infarction/blood , Reference Values , Coronary Artery Disease/genetics , Coronary Artery Disease/blood , Haplotypes , Energy Intake , C-Reactive Protein/analysis , Enzyme-Linked Immunosorbent Assay , Biomarkers/blood , Nutrition Assessment , Sex Factors , Anthropometry , Cross-Sectional Studies , Risk Factors , Analysis of Variance , Age Factors , Statistics, Nonparametric , Stroke/genetics , Stroke/blood , Genotyping Techniques , Homocysteine/blood , Myocardial Infarction/genetics
7.
Arq. bras. cardiol ; 107(2): 131-136, Aug. 2016. tab, graf
Article in English | LILACS | ID: lil-794563

ABSTRACT

Abstract Background: Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD. Objective: To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk. Methods: A total of 212 cases with CHD and 218 controls were enrolled. Methylation at two CpG sites in IL-6 promoter was measured by bisulfite pyrosequencing, and the mean IL-6 methylation was calculated by averaging the methylation measures of the two CpGs. Results: Mean methylation level in IL-6 promoter in CHD cases was significantly lower than that in controls (p = 0.023). Logistic regression analysis showed that IL-6 methylation was inversely associated with the risk of CHD. The odds ratios (ORs) of CHD for subjects in the second and first (lowest) tertile of IL-6 methylation were 1.87 (95% CI = 1.10‑3.20) and 2.01 (95% CI = 1.19-3.38) (ptrend = 0.013), respectively, compared to subjects in the third (highest) tertile. The IL-6 hypomethylation-related risk estimates tended to be stronger for acute myocardial infarction (ptrend = 0.006). CpG position-specific analysis showed that hypomethylation of position 1 conferred a more pronounced increase in CHD risk than that of position 2. Conclusion: These findings suggest that DNA hypomethylation of IL-6 promoter is associated with the increased risk for CHD, especially for acute myocardial infarction. The two distinct CpGs in IL-6 may contribute differently to the development of CHD.


Resumo Fundamento: Interleucina-6 (IL-6) está implicada na patogênese de doença arterial coronariana (DAC), sendo sua expressão associada com redução da metilação de DNA do promotor do seu gene. Entretanto, não há dados sobre metilação do promotor de IL-6 e risco de DAC. Objetivo: Verificar se a metilação do promotor de IL-6 medida no DNA de leucócitos sanguíneos acha-se associada com risco de DAC. Métodos: este estudo arrolou 212 casos com DAC e 218 controles. Metilação em dois sítios de CpG no promotor de IL-6 foi medida por pirosequenciamento de bissulfito, sendo a metilação média de IL-6 calculada pela média das medidas de metilação dos dois CpGs. Resultados: A média do nível de metilação no promotor de IL-6 nos casos de DAC foi significativamente mais baixa do que nos controles (p = 0,023). Análise de regressão logística mostrou associação inversa entre metilação de IL-6 e risco de DAC. As razões de chance (OR) de DAC para indivíduos no segundo e no primeiro (mais baixo) tercis de metilação de IL-6 foram 1,87 (IC 95%: 1,10-3,20) e 2,01 (IC 95%: 1,19-3,38) (ptrend = 0,013), respectivamente, comparadas à de indivíduos no terceiro (mais alto) tercil. As estimativas de risco relacionado à hipometilação de IL-6 tenderam a ser mais fortes para infarto agudo do miocárdio (ptrend = 0,006). Análise com especificidade de posição de CpG mostrou que hipometilação na posição 1 conferiu maior elevação no risco de DAC do que na posição 2. Conclusão: Tais achados sugerem que a hipometilação de DNA do promotor de IL-6 está associada com elevado risco de DAC, especialmente para infarto agudo do miocárdio. Os dois CpGs distintos no promotor de IL-6 podem contribuir de modo diferente para o desenvolvimento de DAC.


Subject(s)
Humans , Male , Female , Aged , Interleukin-6/genetics , Promoter Regions, Genetic , CpG Islands , DNA Methylation , Coronary Disease/genetics , Genetic Predisposition to Disease/genetics , Interleukin-6/metabolism , Sequence Analysis, DNA , Angina, Unstable/genetics , Myocardial Infarction/genetics
9.
Clinics ; 68(1): 75-80, Jan. 2013. graf, tab
Article in English | LILACS | ID: lil-665921

ABSTRACT

OBJECTIVE: Recent studies have shown that circulating microRNAs might be useful, novel biomarkers for the diagnosis of acute myocardial infarction. The aims of this study were to evaluate the expression of cardiac-specific miRNAs (miR-1, -133a, -208b, and -499) in patients with acute myocardial infarction and to compare the diagnostic values of these miRNAs with that of cardiac troponin T. METHODS: Sixty-seven plasma samples obtained from patients with acute myocardial infarction and 32 plasma specimens collected from healthy volunteers were analyzed in this study. The levels of cardiac-specific miRNAs (miR-1, -133a, -208b, and -499) were measured by quantitative reverse transcription-polymerase chain reaction, and the concentrations of plasma cardiac troponin T were measured using electrochemiluminescence-based methods and an Elecsys 2010 Immunoassay Analyzer. RESULTS: The levels of plasma miR-1, -133a, -208b, and -499 were significantly higher in acute myocardial infarction patients (all p<0.001) than in healthy volunteers. The expression of the cardiac-specific miRNAs in acute myocardial infarction patients decreased to close to the baseline levels at the time of hospital discharge (all p>0.05). There were no correlations between the levels of the four circulating miRNAs and the clinical characteristics of the study population (all p>0.05). Furthermore, receiver operating characteristic curve analyses showed that the four plasma miRNAs were not superior to cardiac troponin T for the diagnosis of acute myocardial infarction (all p>0.05). CONCLUSION: Our results demonstrate that circulating miR-1, -133a, -208b, and -499 may be useful biomarkers in acute myocardial infarction patients but that these miRNAs are not superior to cardiac troponin T for the diagnosis of acute myocardial infarction.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , MicroRNAs/blood , Myocardial Infarction/diagnosis , Troponin T/blood , Biomarkers/blood , Epidemiologic Methods , Immunoassay , Luminescent Measurements , Myocardial Infarction/genetics , Predictive Value of Tests , Reference Values , Reverse Transcriptase Polymerase Chain Reaction
11.
Article in English | WPRIM | ID: wpr-175095

ABSTRACT

BACKGROUND/AIMS: Family history (FHx) of coronary heart disease (CHD) is a well-known risk factor for CHD. However, the prognostic implication of FHx has not been established clearly in patients with acute myocardial infarction (AMI). METHODS: In total, 11,612 patients (8,132 males [70%], age 63 +/- 13 years) with first-onset AMI between November 2005 and June 2008 in a nationwide, prospective, multicenter, online registry (the Korea AMI Registry) were analyzed. Clinical characteristics and outcomes (cardiac death and major adverse cardiac events [MACEs]) were assessed according to the presence of FHx. RESULTS: The patients with FHx were younger and included more males. Male patients with FHx included more current smokers and individuals with poor lipid profiles. In all patients, after adjustment using the Cox proportional hazard model, FHx was related to the risk of MACEs (hazard ratio [HR], 1.41; p = 0.009) and cardiac death (HR, 1.56; p = 0.080). The poor prognostic implication of FHx was further augmented in females and a low risk subset of patients. A significant interaction was only found between male and female patients for composite MACEs (p for interaction = 0.057), and between patients with more risk factors (> or = 2 risk factors) and fewer risk factors for cardiac deaths (p for interaction = 0.008). CONCLUSIONS: FHx may be an independent prognostic predictor, especially in female patients and patients with low-risk profile.


Subject(s)
Adult , Aged , Chi-Square Distribution , Coronary Artery Bypass , Coronary Disease/genetics , Female , Genetic Predisposition to Disease , Heredity , Humans , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/genetics , Pedigree , Percutaneous Coronary Intervention , Prognosis , Proportional Hazards Models , Registries , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Sex Factors , Time Factors
12.
Arq. bras. cardiol ; 95(2): 144-152, ago. 2010. ilus, graf, tab
Article in Portuguese | LILACS | ID: lil-557824

ABSTRACT

FUNDAMENTO: O polimorfismo AGT*M235T tem sido associado a elevados níveis séricos de angiotensinogênio (AGT), hipertensão arterial sistêmica e disfunção cardíaca (DC). OBJETIVO: Testar a hipótese de haver associação entre polimorfismo AGT*M235T e o risco de desenvolver disfunção cardíaca (insuficiência cardíaca ou disfunção sistólica ventricular esquerda assintomática) pós-síndrome coronariana aguda (SCA), durante o período de internação hospitalar. MÉTODOS: Foram estudados 363 pacientes (idade média 62 ± 12 anos), sendo 233 (64 por cento) homens e 130 (36 por cento) mulheres, todos da mesma coorte, internados por SCA. Compararam-se dados clínicos e genéticos dos 117 (32,2 por cento) que evoluíram com disfunção cardíaca (grupo caso) com os dos 246 (67,8 por cento), que não desenvolveram tal condição (grupo controle). O polimorfismo AGT*M235T foi determinado por análise de sequenciamento e estava em equilíbrio de Hardy-Weinberg. RESULTADOS: Houve diferença significativa na distribuição dos genótipos nas mulheres, com predomínio do genótipo *235MM no grupo controle (p = 0,001) e do alelo *235T no grupo caso. Em ambos os sexos, nos modelos de regressão logística, o diagnóstico de infarto de parede anterior na admissão foi fator de incremento no risco de DC, enquanto angina instável na admissão, ausência do alelo *235T, glicemia < 100 mg/dl, uso de betabloqueador, creatinina sérica < 1,5 mg/dl, faixa de frequência cardíaca > 60 e < 90 bpm e tabagismo atual foram fatores de redução do risco de DC. CONCLUSÃO: Este estudo sugere que a ausência do alelo *235T do AGT contribui para a redução do risco de disfunção cardíaca pós-síndrome coronariana aguda.


BACKGROUND: AGT*M235T polymorphism has been associated with high serum angiotensinogen (AGT) levels, systemic hypertension and cardiac dysfunction (CD). OBJECTIVE: To test the hypothesis of AGT*M235T polymorphism being associated with the risk of developing cardiac dysfunction (heart failure or asymptomatic left ventricular systolic dysfunction) after acute coronary syndrome (ACS) during hospitalization. METHODS: A total of 363 patients (mean age of 62 ± 12 years), of whom 233 (64 percent) were men and 130 (36 percent) were women, all from the same cohort and hospitalized for ACS, were studied. Clinical and genetic data from the 117 (32.2 percent) patients who developed cardiac dysfunction (case group) were compared to those of the 246 (67.8 percent) who did not develop this condition (control group). The AGT*M235T polymorphism was determined by sequence analysis and was in Hardy-Weinberg equilibrium. RESULTS: There was a significant difference in the distribution of genotypes among women, with a predominance of the *235MM genotype in the control group (p = 0.001) and of the *235T allele in the case group. In the logistic regression models, the diagnosis of anterior wall myocardial infarction at admission was related to an increased risk of CD in both genders, whereas unstable angina at admission.; absence of the *235T allele; blood glucose <100 mg/dl; use of betablocker; serum creatinine level < 1.5 mg/dl;heart rate range > 60 and < 90 bpm; and current cigarette smoking were related to a lower risk of CD. CONCLUSION: This study suggests that the absence of the AGT *235T allele contributes to a reduced risk of cardiac dysfunction after acute coronary syndrome.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Acute Coronary Syndrome/genetics , Angiotensinogen/genetics , Polymorphism, Genetic , Alleles , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Angiotensinogen/blood , Case-Control Studies , Echocardiography , Genotype , Hypertension/genetics , Logistic Models , Myocardial Infarction/genetics
13.
Article in English | IMSEAR | ID: sea-135476

ABSTRACT

Background & objectives: Paraoxonase (PON) is an HDL associated ester hydrolase with an ability to retard LDL oxidation in vitro by preventing lipid peroxide generation. The population variability in enzyme activity is attributed to polymorphisms in paraoxonase gene. For example, polymorphism at codon 192 and 55 of the paraoxonase gene has been reported to be associated with coronary heart disease (CAD) and diabetes among different ethnic groups. The present study looks at PON192 and 55 polymorphism among hospitalized Asian Indian patients with myocardial infarction (MI) and their association with circulating oxidized LDL and antioxidant status. Methods: One hundred and twenty four consecutive patients of acute myocardial infarction and 221 age-matched controls were recruited for the study. Oxidized LDL was measured in serum by ELISA and total antioxidant levels by the 2,2’-azino-bis-(3 ethyl benzothiozoline-6-sulfonate) (ABTS) method. Other known cardiovascular risk factors, apolipoprotein B, apolipoproteinA1, lipoprotein(a), hsCRP and homocysteine were also measured. Paraoxonase gene polymorphism at codon 192 and 55 were analyzed by PCR-RFLP. Results: Patients with MI had significantly higher oxidized LDL (P<0.05) and lower total antioxidant capacity (P<0.001) as compared to controls. Oxidized LDL correlated with total cholesterol, LDL and Apo B in patients. B allele frequency of the codon 192 polymorphism in paraoxonase gene was higher in cases as compared to controls and odds ratio of developing the MI with BB genotype versus AA genotype was 2.37, (P=0.044). Codon 55 polymorphism in paraoxonase gene was not associated with CAD. There was no difference in oxidized LDL between the different genotypes of PON192 and PON55. Interpretation & conclusions: Although PON192 polymorphism was associated with CAD, no correlation of PON192 or 55 polymorphism was found with oxidized LDL suggesting that presence of other antioxidant factors may be of equal importance in preventing LDL oxidation.


Subject(s)
Aryldialkylphosphatase/genetics , Base Sequence , DNA Primers , Humans , Lipoproteins, LDL/blood , Myocardial Infarction/blood , Myocardial Infarction/genetics , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length
14.
Cir. & cir ; 78(1): 93-97, ene.-feb. 2010.
Article in Spanish | LILACS | ID: lil-565702

ABSTRACT

La enfermedad arterial coronaria (EAC) es la primera causa de muerte en todo el mundo y representa un problema de salud pública en México. El infarto agudo del miocardio (IAM) representa la principal complicación trombótica de la EAC. Aproximadamente 9 % de los nuevos casos está constituido por sujetos menores de 45 años. El IAM se produce por el desarrollo de un trombo en el sitio de la placa aterosclerosa, generando oclusión arterial súbita con isquemia y muerte celular. El IAM resulta de la interacción entre factores genéticos y ambientales. Existen diversos factores de riesgo modificables como la hipertensión arterial, la diabetes mellitus, el tabaquismo, la obesidad y la hipercolesterolemia asociados con el IAM. Sin embargo, numerosos pacientes con IAM no presentan factores de riesgo modificables. En la última década se han identificado variantes genéticas en las proteínas relacionadas con los sistemas de coagulación y fibrinólisis, receptores plaquetarios, disfunción endotelial, flujo sanguíneo anormal, metabolismo de la homocisteína, estrés oxidativo, los cuales se asocian a desarrollo del IAM. La identificación de los polimorfismos asociados a la enfermedad arterial coronaria permitirá desarrollar mejores estrategias de tratamiento e identificación de individuos con alto riesgo para EAC y medidas preventivas en etapas tempranas.


BACKGROUND: Coronary artery disease (CAD) is the first cause of death worldwide and represents a public health issue in our country. Acute myocardial infarction (AMI) represents the main thrombotic complication of CAD. Approximately 9% of the new events of MI occur in patients <45 years of age. DISCUSSION: AMI is produced by development of a thrombus at the site of an atherosclerotic plaque that initiates abrupt arterial occlusion, with ischemia and cell death. AMI results from the interaction of gene-environment factors. There are several modifiable factors such as hypertension, diabetes, smoking, obesity, and hypercholesterolemia associated with AMI. However, in a large number of patients with AMI, modifiable risk factors are not present. In the last decade, several genetic variants (polymorphisms) have been identified associated with AMI in genes related to coagulation proteins, fibrinolytic system, platelet receptors, homocysteine metabolism, endothelial dysfunction, abnormal blood flow and oxidative stress. CONCLUSIONS: Identifying the genes associated with CAD will allow us to develop more efficacious treatment strategies and will also help to identify at-risk subjects, thereby enabling the introduction of early preventive measures. Thus, many research efforts continue to address the identification of acquired and inherited risk factors of this complex disease.


Subject(s)
Humans , Male , Female , Adult , Hemostasis/genetics , Myocardial Infarction/etiology , Thrombophilia/genetics , Endothelium, Vascular/pathology , Blood Coagulation Factors/genetics , Genetic Predisposition to Disease , Platelet Membrane Glycoproteins/genetics , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/genetics , Myocardial Infarction/blood , Myocardial Infarction/genetics , Nitric Oxide Synthase Type III/deficiency , Nitric Oxide Synthase Type III/genetics , Polymorphism, Genetic , Blood Platelets/pathology , Risk Factors , Thrombophilia/complications
15.
Journal of Tehran Heart Center [The]. 2010; 5 (3): 116-121
in English | IMEMR | ID: emr-98602

ABSTRACT

Myocardial infarction [MI] and its major determinant, coronary artery disease [CAD], are complex diseases arising from the interaction between several genetic and environmental factors. Until recently, the genetic basis of these diseases was poorly understood. Genome-wide genetic association studies have afforded a comprehensive insight into the association between genetic variants and diseases. To date, seven genome-wide association studies have been conducted in CAD/MI, identifying thirteen genomic regions at which common genetic variants influence the predisposition to these diseases. This review article summarizes the progress achieved in the genetic basis of MI and CAD by means of genome-wide association studies and the potential clinical applications of these findings


Subject(s)
Humans , Myocardial Infarction/genetics , Coronary Artery Disease/genetics , Risk Factors
16.
Egyptian Journal of Hospital Medicine [The]. 2009; 34 (March): 69-77
in English | IMEMR | ID: emr-162106

ABSTRACT

The present work aims to test the association of angiotensin converting enzyme [ACE] gene insertion/ deletion [I/D] polymorphism in patients with myocardial infarction [MI]. The study comprised 79 Egyptian cases with MI. Their mean age was 54.4 +/- 9.9 years including 60 [75%] males and 19 [24.1%] females, 23 [29.1%] were smokers, 21 [26.6%] had a positive family history of MI, 25 cases [31.6%] were diabetic, 16 cases [20.3%] were hyperlipidemic. For comparison, 238 healthy subjects of nearly matched age and sex, with no history of any cardiac diseases were taken as a control group. For all subjects, DNA testing for ACE gene I/D polymorphism was done using PCR amplification to detect both D and I alleles followed by a second run PCR specific for the I allele for cases typed as DD in the first run. Cases had higher frequency of DD [29.1%] and ID [62%] than II [8.9%] genotype with a higher frequency of D allele than I allele [64.4% vs 33.6%]. Compared to controls, cases had significantly higher frequency of ID genotype [62% versus 47.5%, P < 0.05]. Cases with low risk factors had a higher frequency of ID genotype compared to controls [66.7% vs 47.5%, P = 0.002]. The same was, also, found in the high risk group but with a lower level of significance [63.6% vs 47.5%, P = 0.041]. ACE gene polymorphism is probably a risk factor for ischemic heart disease among Egyptian cases particularly if integrated with other environmental and genetic risk factors


Subject(s)
Humans , Female , Male , Adult , Middle Aged , Aged , Polymorphism, Genetic , Heart Diseases/genetics , Myocardial Infarction/genetics , Genes , Ischemia , Polymerase Chain Reaction , Hyperlipidemias , Diabetes Mellitus
17.
Rev. méd. Chile ; 136(11): 1371-1380, nov. 2008. tab
Article in Spanish | LILACS | ID: lil-508956

ABSTRACT

Background: ß adrenergic receptors (AR) are highly polymorphic and important regulators of cardiovascular homeostasis. Among these, ß1 and ß2 AR regulate cardiac contractility and frequency and are important pharmacological targets. Aim: To evaluate genotype and gene-gene interaction between ß1-AR Arg389Gly and ß2-AR ArglSGly GlnZ7Gly and Thrl 64Ile polymorphisms, as risk factors for HF. Material and methods: Eighty chronic HF patients and eighty-eight controls matched by age and sex were genotyped for ß1 -AR Arg389Gly ß2-AR ArgWGly, GlnZ7Glu and Thr164Ile polymorphisms. Results: The presence of ß2-AR Glu afiele was a risk predictor for HF (odds ratio (OR) =2.81; 95 percent confidence intervals (CI) =1.49-5.31). Interactions that increased the risk for HF were found in patients carrying at least one of the ß2-AR Glu and ß2-AR Gly allele (OR =3.81; 95 percent CI =1.50-0.70) and ß2-AR Glu and ß1 -AR Gly allele combination (OR =5.51; 95 percent CI =2.19-13.86). Furthermore, the frequency of ß2-AR Glu allele was higher among patients with a history ofacute myocardial infarction (with infarction: 0.534, without: 0.313, p =0.01). Conclusions: ß2-AR Glu allele could be a risk predictor for HF. This risk could be enhanced by the additional presence of ß2-AR GlyW or ß1-AR Arg389 alleles. The frequency of ß2-AR Gln27 Glu allele was higher among patients with a history of myocardial infarction.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Heart Failure/genetics , Myocardial Infarction/genetics , Polymorphism, Genetic/genetics , Receptors, Adrenergic, beta-1/genetics , /genetics , Case-Control Studies , Chronic Disease , Gene Frequency , Genetic Predisposition to Disease , Genotype , Risk Factors , Severity of Illness Index , Young Adult
18.
Rev. biol. trop ; 54(1): 1-11, mar. 2006. tab
Article in English | LILACS | ID: lil-484689

ABSTRACT

Eight common polymorphisms of known myocardial infarction (MI)risk factors (factor V Leiden (FVL), factor V HR2 (FVHR2), factor II 20210G>A (FII), factor VII IVS7 (FVII IVS7), factor VII Arg353Gln (FVII), factor XIII Val34Leu (FXIII), Methylenetetrahydrofolate reductase C677T (MTHFR), Angiotensin Converting Enzyme (ACE))and environmental risk factors were analyzed in a MI patients of Costa Rica.This case-control study included 186 MI subjects,95 of them <45 years and 201 age and sex matched controls.With the use of PCR method the polymorphisms were detected and through interviews additional information was collected.Hypercholesterolemia and smoking were associated with a significant risk in younger patients.High fibrinogen level was an important risk factor and interaction with smoking was detected.Mainly,the genotype 34LeuLeu of FXIII showed significant protective effect,(OR 0.32,95%CI 0.13-0.80)while the other polymor- phisms showed no significant difference between the cases and the controls.Carriers of FVII (OR 2.75,95%CI 1.07-7.02)and FXIII (OR 4.20,95%CI 2.03-8.67)polymorphisms showed interaction with fibrinogen in the sta- tistical analysis.It was concluded that there was an important interaction between the common risk factors and the polymorphisms (FVII;FXIII)in the development of MI.This is one of the first reports in a Latin-American population dealing with these molecular markers and MI.


Se estudiaron ocho polimorfismos comunes asociados como factores de riesgo para el infarto al miocardio (IM):factor V Leiden (FVL),factor VHR2 (FVHR2), factor II 20210G>A (FII),factor VII IVS7 (FVII IVS7), factor VIIArg353Gln (FVII),factor XIIIVal34Leu (FXIII), metilentetrahidrofolato reductase C677T (MTHFR), enzima convertidora de la angiotensina (ACE) y factores ambientales de riesgo,en pacientes costarricenses.Este es un estudio de casos y controles,donde participan 186 pacientes,95 de ellos con edades <45 años y 201 sujetos controles.Se utilizó la técnica de reacción en cadena de la polimerasa (PCR)y por medio de entrevistas personales se recolectó información epidemiológica adicional.Se encontró que la hipercolesterolemia y el fumado estan asociados como factores de riesgo en los pacientes jóvenes.Niveles elevados del fibrinógeno fueron detectados como un factor de riesgo importante y se observo interacción entre fumado y estos valores aumentados de fibrinógeno. El genotipo 34LeuLeu del FXIII presentó un efecto protector significante mientras que los otros polimorfimos estudiados no mostraron diferencia estadísticamente significativa entre los casos y controles. Los polimorfismos del FVII y FXIII demostraron interación con el fibrinógeno,según el análisis estadístico aplicado. Se evidencia, la interación entre factores de riesgo común y ciertos polimorfismos (FVII;FXIII)en la patogénesis del IM.Este es uno de los primeros informes sobre estos marcadores moleculares y su asociación con IM en una población latinoamericana.


Subject(s)
Humans , Male , Female , Middle Aged , Myocardial Infarction/genetics , Polymorphism, Genetic , Case-Control Studies , Costa Rica , Genetic Predisposition to Disease , Genetic Markers/genetics , Risk Factors
19.
Arch. cardiol. Méx ; 75(3): 363-370, jul.-sep. 2005. ilus, tab
Article in Spanish | LILACS | ID: lil-631897

ABSTRACT

Para la biología de hoy las vías de señalización intracelular que controlan los procesos entre la vida y la muerte celular son de gran interés. Al respecto, el NF-κB destaca como un factor de transcripción decisivo de respuesta rápida que participa en la activación de las vías de señalización de la muerte celular programada. Lo relevante es que sus efectos tienen consecuencias en el desarrollo normal y/o la homeostasis en muchas células o tejidos, que incluyen entre otros al sistema inmune, los folículos capilares, apéndices epidermales, el riñon y el sistema nervioso. En esta revisión analizamos el papel central que juega el factor de transcripción NF-κB en el funcionamiento normal de la célula cardíaca y sus implicaciones en algunas de las patologías cardíacas más frecuentes como: el daño por isquemia-reperfusión, la isquemia precondicionada, la hipertrofia, la aterosclerosis, y el paro cardíaco. El NF-κB comúnmente funciona como un agente citoprotector, aunque hay algunos casos en los cuales resulta ser pro-apoptótico dependiendo del estímulo y del contexto celular. Se han logrado avances significativos a nivel molecular, que han permitido entender su modo de acción y el papel interactivo que juega con otros factores claves. Estos estudios han identificado muchos genes anti-apoptóticos y pro-apoptóticos regulados por la actividad del NF-κB abriendo novedosas aproximaciones que se pueden hacer sobre sus efectos en el desarrollo de patologías cardíacas.


The signaling pathways that control the life-death switch of a cell are a prime interest in Modern Biology. To this respect, NF-κB has emerged as a decisive transcription factor in the cell's response to apoptotic challenge and its effects on apoptosis have far-reaching consequences for normal development and/or homeostasis in many cells and tissues, including the immune system, hair follicles, and epidermal appendages, the liver, and nervous system. In this review we analyze the pivotal role of the transcription factor NF-κB in the normal functioning of the cardiac cell and its implication on some of the most frequent cardiac pathologies, such as ischemia-reperfusion injury, ischemic precondition, hypertrophy, atherosclerosis and cardiac arrest. While NF-κB is commonly found to be cytoprotective, there are a number of instances where it is proapoptotic depending on the inducing stimulus and the cell context. Significant progress has been made in understanding its mode of action and its interplay with other key factors. These studies identified many anti- and pro-apoptotic NF-κB regulated genes that mediate its activity, these important new insights fuel hope that novel approaches will be developed to control the effects of NF-κB in cardiac pathologies.


Subject(s)
Animals , Humans , Rabbits , Rats , Apoptosis , Myocytes, Cardiac , NF-kappa B/physiology , Apoptosis/genetics , Apoptosis/physiology , Cells, Cultured , Cardiomegaly/physiopathology , Coronary Artery Disease/etiology , Coronary Artery Disease/genetics , Coronary Artery Disease/pathology , Coronary Artery Disease/physiopathology , Disease Models, Animal , Disease Progression , Heart Arrest , Homeostasis , Ischemic Preconditioning, Myocardial , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardial Ischemia/genetics , Myocardial Ischemia/pathology , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Myocytes, Cardiac/physiology , NF-kappa B/genetics , Oxidative Stress , Phenotype , Time Factors
20.
Rev. Assoc. Med. Bras. (1992) ; 51(3): 164-169, maio-jun. 2005. tab
Article in Portuguese | LILACS | ID: lil-411189

ABSTRACT

OBJETIVO: Estudar o efeito do polimorfismo M235T do gene do angiotensinogênio na doença arterial coronariana e na sua gravidade em pacientes com e sem infarto agudo do miocárdio. MÉTODOS: Estudo transversal com 305 indivíduos de raça branca que foram alocados em 2 grupos. O primeiro com 201 pacientes com doença arterial coronariana comprovada pela angiografia (lesão obstrutiva > 50 por cento), sendo 110 com infarto agudo do miocárdio e 91 sem infarto. O segundo, 104 indivíduos controles com artérias coronárias normais. O polimorfismo M235T do angiotensinogênio foi analisado através da genotipagem pela reação em cadeia da polimerase seguida da digestão pela enzima de restrição. RESULTADOS: A freqüência dos genótipos TT, MT e MM do angiotensinogênio não foi estatisticamente diferente entre os pacientes com doença arterial coronariana e os controles (chi2 = 0,123; p = 0,939) bem como nos grupos de infartados e não infartados (chi2 = 2,171; p = 0,338). O risco relativo de desenvolver doença arterial coronariana e de apresentar infarto analisado entre os genótipos TT vs MM, MT vs MM e TT+MT vs MM não foi significante. A análise da gravidade da doença aterosclerótica no grupo de pacientes com doença arterial coronariana mostrou não haver correlação com os genótipos; resultado semelhante foi encontrado na comparação entre os grupos com e sem infarto. CONCLUSÕES: Não há associação entre o polimorfismo M235T do gene do angiotensinogênio com a doença arterial coronariana, com a sua gravidade e nem com o infarto agudo do miocárdio.


Subject(s)
Female , Humans , Male , Middle Aged , Angiotensinogen/genetics , Coronary Artery Disease/genetics , Gene Frequency , Myocardial Infarction/genetics , Polymorphism, Genetic , Cross-Sectional Studies , Genotype , Phenotype
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