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The interleukin-17 (IL-17) has a crucial role during inflammation and has been associated with cardiovascular diseases, but its role in epigenetics is still poorly understood. Therefore, the aim of this study was to evaluate the DNA methylation status of the IL-17A gene promoter to establish whether it may represent a risk factor for subclinical atherosclerosis (SA) or clinical coronary artery disease (CAD). We included 38 patients with premature CAD (pCAD), 48 individuals with SA, and 43 healthy controls. Methylation in the CpG region of the IL-17A gene promoter was assessed via methylation-specific polymerase chain reaction (MSP). Individuals with SA showed increased methylation levels compared to healthy controls and pCAD patients, with p < 0.001 for both. Logistic regression analysis showed that high methylation levels represent a significant risk for SA (OR = 5.68, 95% CI = 2.38-14.03, p < 0.001). Moreover, low methylation levels of the IL-17A gene promoter DNA represent a risk for symptomatic pCAD when compared with SA patients (OR = 0.16, 95% CI = 0.06-0.41, p < 0.001). Our data suggest that the increased DNA methylation of the IL-17A gene promoter is a risk factor for SA but may be a protection factor for progression from SA to symptomatic CAD.
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Hypertension is a major risk of morbidity and mortality in patients when it is uncontrolled. In spite of improved therapies currently available for blood pressure control, their complications are far away from being accomplished. Therefore, chronic renal failure is frequently observed in hypertensive patients. Thus, insights on mechanisms that may contribute to arterial pressure control should be studied to prevent life-threatening cardiovascular disorders. Purinergic receptors have been recognized in the physiopathology of hypertension; this review summarizes their participation in the renal abnormalities of the kidney in hypertension. Several studies have suggested the activation of renal purinergic receptors under an elevated interstitial ATP milieu as a fundamental pathway that leads to generation and maintained hypertension. Elevated ATP concentration alters fundamental mechanisms involved in the long-term control of blood pressure such as pressure natriuresis, autoregulation of glomerular filtration rate and renal blood flow, as well as increased tubule-glomerular feedback responses, overall, these alterations decrease sodium excretion; in addition, the expression of ATP receptors is modified. Under a genetical background, ATP induces the production of vasoactive compounds, decreases renal function and induces tubulointerstitial injury before glomerular damage. Simultaneously, a deleterious interaction between angiotensin II and purinergic receptors lead to the progression of renal damage.
La hipertensión arterial descontrolada es un factor de riesgo muy relevante para el desarrollo de complicaciones cardiovasculares graves. A pesar de los recursos disponibles en la actualidad, el control de la hipertensión arterial y sus complicaciones dista mucho de lograrse. Por ello, sus secuelas continúan siendo catastróficas, como la insuficiencia renal crónica. De ahí la relevancia de reconocer factores que pudieran modificarse para evitar esta complicación. Recientemente se ha propuesto que los receptores purinérgicos contribuyen en forma importante en las alteraciones renales que ocurren en la hipertensión arterial; en esta revisión se resume brevemente su papel. En varios estudios se ha demostrado que cuando existen concentraciones elevadas de ATP en el intersticio renal, la activación de los receptores purinérgicos constituye una vía fundamental en la generación y la persistencia de hipertensión arterial. Las concentraciones elevadas de ATP alteran mecanismos fundamentales asociados en el control de la presión arterial, como el mecanismo de natriuresis de presión, la autorregulación del flujo renal y la filtración glomerular, así como el aumento en la sensibilidad del mecanismo de retroalimentación tubuloglomerular. La alteración de estos mecanismos contribuye a la disminución de la excreción urinaria de sodio. Además, se modifica la expresión de receptores de ATP (purinérgicos). Bajo la influencia de alteraciones genéticas, el ATP estimula la producción de compuestos vasoactivos y en conjunto producen una disminución de la función renal y lesión tubulointersticial antes de que se lesione el glomérulo. Al mismo tiempo, la interacción de la angiotensina II y los receptores purinérgicos favorece la progresión del daño renal.
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Cholesterol-7-alpha hydroxylase (CYP7A1) is a key enzyme in the synthesis of bile salts, and its activity can contribute to determining cholesterol levels and, consequently, the risk of developing coronary atherosclerotic disease. We evaluated whether seven (rs3808607 G/T, rs9297994 G/A, rs10504255 A/G, rs8192870 G/T, rs2081687 C/T, rs1457043 C/T, and rs10107182 C/T) polymorphisms located in the promoter and enhancer regions of the CYP7A1 gene, which have not been sufficiently explored, are candidates of risk markers of acute coronary syndrome (ACS) in the Mexican population. These polymorphisms were determined in a group of 1317 patients with ACS and 1046 control subjects. The results showed that, under different inheritance models, the alleles rs9297994 G, rs10504255 G, rs8192870 T, rs2081687 T, and rs10107182 C were significantly associated with an increased risk of ACS (pC < 0.05). In addition, the incidence of dyslipidemia among patients with ACS, notably high total cholesterol and LDL-cholesterol, and low HDL-cholesterol plasma levels, were more frequent in carriers of the same five risk alleles associated with ACS (p < 0.05). There was also an unexpected increased incidence of type 2 diabetes mellitus (T2DM) in patients with ACS who are homozygous for the rs2081687 T, rs9297944 G, rs10504255 G, and rs10107182 C alleles of the CYP7A1 gene, suggesting that such gene variants enhance the development of coronary complications in patients with diabetes (p < 0.05). In summary, our study demonstrated that five polymorphisms situated in the promoter and enhancer regions of the CYP7A1 gene are associated with the risk of ACS and higher incidences of dyslipidemia and T2DM in Mexican patients with ACS.
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BACKGROUND: In the present study, we evaluated whether DEFB1 gene polymorphisms are associated with the presence of coronary artery disease (CAD). METHODS: Two rs11362 A/G, and rs1800972 C/G gene polymorphisms of DEFB1 gene were genotyped by 5'exonuclease TaqMan assays in 219 patients with CAD and 522 control individuals. RESULTS: The distribution of rs1800972 C/G polymorphisms was similar in patients with CAD and healthy controls. Nonetheless, under the co-dominant, dominant, recessive, and additive models, the AA genotype of the rs11362 A/G polymorphism was associated with the risk of developing CAD (OR = 1.89 pCCo-Dom = 0.041, OR = 1.46, pCDom = 0.034, OR = 1.69, pCRes = 0.039, and OR = 1.37, pCAdd = 0.012, respectively). In addition, the linkage disequilibrium showed that the 'AG' haplotype was associated with an increased risk of developing CAD (OR = 1.23, p = 0.042). According, with the Genotype-Tissue Expression (GTEx) consortium data, the rs11362 AA genotype is associated with a low mRNA expression of the ß-defensin-1 in tissues, such as artery aorta, artery coronary, heart left ventricle, and heart atrial appendage (p < 0.001). CONCLUSION: This study demonstrates that rs11362 A/G polymorphism of the DEFB1 gene is involved in the risk of developing CAD, and with a low RNA expression of the ß-defensin-1 in heart tissue.
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Resumen Los esfingolípidos (esfingomielina, glucolípidos y gangliósidos) se localizan en las membranas celulares, el plasma y las lipoproteínas. En pacientes con enfermedades cardiovasculares, renales y metabólicas, el perfil de los esfingolípidos y sus metabolitos (ceramida, esfingosina y esfingosina-1-fosfato) se modifica, y estos cambios pueden explicar las alteraciones en algunas respuestas celulares, como la apoptosis. Además, se ha sugerido que la esfingosina y la esfingosina-1-fosfato previenen la COVID-19. En esta revisión también se mencionan brevemente las técnicas que permiten el estudio de los esfingolípidos y sus metabolitos.
Abstract Sphingolipids (sphingomyelin, glycolipids, gangliosides) are located in cell membranes, plasma, and lipoproteins. In patients with cardiovascular, renal, and metabolic diseases, the profile of sphingolipids and their metabolites (ceramide, sphingosine, and sphingosine-1-phosphate) is modified, and these changes may explain the alterations in some cellular responses such as apoptosis. Furthermore, sphingosine and sphingosine-1-phosphate have been suggested to prevent COVID-19. This review also briefly mentions the techniques that allow us to study sphingolipids and their metabolites.
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Abstract Objective: We evaluated whether cholesteryl ester transfer protein (CETP) gene polymorphisms are associated with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent. Methods: Two polymorphisms of the CETP gene [−971 A/G (rs4783961), and Taq1B A/G (rs708272)] were genotyped by 5'exonuclease TaqMan assays in 219 patients with CAD (66 patients with restenosis and 153 without restenosis) and 607 control individuals. Results: The distribution of polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under dominant model, the G allele of the Taq1B A/G polymorphism was associated with increased risk of CAD (odds ratio [OR] = 1.48, pCDom = 0.032). In the same way, under codominant, dominant, and additive models, the A allele of the −971 A/G polymorphisms was associated with an increased risk of developing CAD (OR = 2.03, pCCo-dom = 0.022, OR = 1.83, pCDom = 0.008, and OR = 1.39, pCAdd = 0.011, respectively). In addition, the linkage disequilibrium showed that the "AG" haplotype was associated with increased risk of developing CAD (OR = 1.28, p = 0.03). Conclusion: This study demonstrates that CETP Taq1B A/G and CETP −971 A/G polymorphisms are associated with an increased risk of developing CAD, but no association with restenosis was observed.
Resumen Objetivo: Evaluamos si los polimorfismos del gen CETP están asociados con la presencia de enfermedad arterial coronaria (EAC) y/o restenosis en pacientes con stent coronario. Métodos: En este estudio se genotiparon dos polimorfismos del gen CETP [−971 A/G (rs4783961) y Taq1B A/G (rs708272)] mediante ensayos de 5'exonucleasa TaqMan en 219 pacientes con EAC (66 pacientes con restenosis y 153 sin restenosis), y 607 individuos de control. Resultados: La distribución de polimorfismos fue similar en pacientes con y sin restenosis. Sin embargo, cuando se comparó todo el grupo de pacientes (con y sin restenosis) con controles sanos, bajo el modelo dominante el alelo G del polimorfismo Taq1B A/G se asocia con un mayor riesgo de EAC (OR = 1.48, pCDom = 0.032). De la misma manera, bajo los modelos co-dominante, dominante y aditivo, el alelo A de los polimorfismos −971 A/G se asocia con un mayor riesgo de desarrollar EAC (OR = 2.03, pCCo-dom = 0.022, OR = 1.83, pCDom = 0,008 y OR = 1.39, pCAdd = 0.011, respectivamente). Adicionalmente, el desequilibrio de ligamiento mostró que el haplotipo "AG" se asocia con un mayor riesgo de desarrollar EAC (OR = 1.28, p = 0.03). Conclusión: En resumen, este estudio demuestra que los polimorfismos CETP Taq1B A/G y CETP −971 A/G están asociados con un mayor riesgo de desarrollar CAD, pero no se observó asociación con restenosis.
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ABSTRACT Background: Previous studies have shown an association between polymorphisms of the BAT1-NF-κB inhibitor-like-1 (NFKBIL1)-LTA genomic region and susceptibility to myocardial infarction and acute coronary syndrome (ACS). Objective: The objective of the study was to study the role of three polymorphisms in the BAT1, NFKBIL1, and LTA genes on the susceptibility or protection against ACS; we included a group of cases-controls from Central Mexico. Methods: The BAT1 rs2239527C/G, NFKBIL1 rs2071592T/A, and LTA rs1800683G/A polymorphisms were genotyped using a 5' TaqMan assay in a group of 625 patients with ACS and 617 healthy controls. Results: Under a recessive model, the BAT1 -23C/G (rs2239527) polymorphism showed an association with protection against ACS (odds ratio = 0.56, and p-corrected = 0.019). In contrast, the genotype and allele frequencies of the NFKBIL1 rs2071592T/A and LTA rs1800683G/A polymorphisms were similar between ACS patients and controls and no association was identified. Conclusion: Our data suggest an association between the BAT1 -23C/G polymorphism and protection against ACS in Mexican patients.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , RNA Helicases DEAD-box/genética , Síndrome Coronariana Aguda/genética , Infarto do Miocárdio/genética , Estudos de Casos e Controles , Linfotoxina-alfa/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Adaptadoras de Transdução de Sinal/genética , Frequência do Gene , Genótipo , MéxicoRESUMO
The I/D insertion/deletion polymorphism of the angiotensin-converting enzyme has been related to hypertension. This polymorphism also seems to have gender related implications. Angiotensin II contributes to the production and release of oxygen reactive species that react with nitric oxide, inactivating its effects. Objective: To establish whether the ACE I/D polymorphism correlates with nitric oxide plasma metabolites in healthy men and women. Methods: Among 896 subjects between 18 and 30 years of age range, 138 fulfilled inclusion criteria. The polymorphism was identified by polymerase chain reaction, and blood nitric oxide metabolites were analyzed following the method described by Bryan. Results: Both systolic and diastolic arterial pressures were higher in men than in women (107/67 vs. 101/65 mmHg, p < 0.001). In terms of the ACE gene, there were differences in the concentration of nitric oxide metabolites in men with the I/D and D/D genotypes when compared to carriers of the I/I genotype (33.55 and 29.23 vs. 53.74 pmol/ml; p = <0.05), while there were no significant differences in women when compared by genotype. Men with the D/D genotype had higher systolic blood pressure than I/D carriers (111 vs. 104 mmHg, p < 0.05). We observed no arterial blood pressure differences in women when grouped by ACE genotype. Conclusions: The ACE D/D genotype was associated with nitric oxide metabolite levels and systolic blood pressure in clinically healthy men while it had no effect in women.
El polimorfismo inserción/deleción del gen de la enzima convertidora de la angiotensina (polimorfismo I/D de la ECA), se relaciona con hipertensión y sus efectos podrían estar asociados al género. La angiotensina II contribuye a la producción y liberación de especies reactivas de oxígeno, que reaccionan con el óxido nítrico (ON), inactivándolo. Objetivo: Conocer si existen diferencias en la concentración de metabolitos de ON en hombres y mujeres sanos que puedan estar influidas por el polimorfismo I/D de la ECA. Métodos: De 896 sujetos de entre 18 y 30 años, 138 cumplieron los criterios de inclusión. El polimorfismo fue identificado usando reacción en cadena de la polimerasa y los metabolitos de ON fueron analizados en sangre usando el método de Bryan. Resultados: Las presiones sistólica y diastólica fueron más elevadas en hombres que en mujeres (107/67 vs. 101/65 mmHg p < 0.001). En relación con el genotipo, existieron diferencias significativas en la concentración de metabolitos de ON en los hombres con genotipos I/D, D/D comparados con los portadores del genotipo I/I (33.55 y 29.23 vs. 53.74 pmol/ml, respectivamente; p = <0.05). No hubo diferencias significativas en las mujeres portadoras de los diferentes genotipos. Respecto a la presión arterial, los hombres con genotipo D/D presentaron mayor presión arterial sistólica que aquellos portadores de I/D (111 vs. 104 mmHg, p < 0.05). En las mujeres no se observaron diferencias significativas comparándolas por genotipo. Conclusiones: El genotipo D/D de la ECA está asociado con el nivel de metabolitos de ON en plasma y la presión arterial sistólica en hombres clínicamente sanos; esta asociación no se observa en las mujeres.
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Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Pressão Sanguínea , Óxido Nítrico/sangue , Polimorfismo Genético , Peptidil Dipeptidase A/genética , Genótipo , México , Óxido Nítrico/metabolismoRESUMO
Objective: The objective of this study was to establish the role of the TLR-4 gene polymorphisms in individuals in risk of developing ACS. Methods: The study included 457 Mexican patients with ACS and 283 control individuals. The TLR-4 Asp299Gly and TLR-4 Thr399Ile single nucleotide polymorphisms were genotyped using 5' exonuclease TaqMan genotyping assays on an 7900HT Fast real-time PCR system according to manufacturer's instructions (Applied Biosystems, Foster City, USA). Results: The results obtained in this study showed that the frequency of the two polymorphisms (TLR-4 Asp299Gly and TLR-4 Thr399Ile) studied were similar between patients with ACS and healthy controls. Multiple logistic regression analysis showed that the largest risk factor for ACS development was given by smoking (11.88-fold increased risk), hypertension (4.32-fold increased risk), type II diabetes (3.44-fold increased risk), gender (2.32-fold increased risk), and dyslipidemia (1.52-fold increased risk). Conclusion: The Asp299Gly and Thr399Ile polymorphisms were not associated with susceptibility to ACS in the Mexican population.
Objetivo: El objetivo de este estudio fue establecer el papel de los polimorfismos del gen TLR-4 en individuos en riesgo de desarrollar síndrome coronario agudo (SCA). Métodos: El estudio incluyó a 457 pacientes mexicanos con SCA y 283 individuos como grupo control. Los polimorfismos de un solo nucleótido TLR-4 Asp299Gly y TLR-4 Thr399Ile fueron determinados usando ensayos TaqMan 5' exonucleasa en un equipo tiempo real 7900HT (Fast real-time PCR system) de acuerdo con instrucciones del fabricante Applied Biosystems, Foster City, EE.UU. Resultados: Los resultados obtenidos mostraron que las frecuencias de los 2 polimorfismos (TLR-4Asp299Gly y TLR-4 Thr399Ile) estudiados fueron similares entre pacientes con SCA e individuos control. No obstante, el análisis de regresión logística mostró que los factores de mayor riesgo para desarrollar SCA se debieron a tabaquismo (incrementa 11.88 veces el riesgo), hipertensión (incrementa 4.32 veces el riesgo), diabetes tipo 2 (incrementa 3.44 veces el riesgo), género (incrementa 2.32 veces el riesgo), y la dislipidemia (incrementa 1.52 veces el riesgo). Conclusión: Determinamos que los polimorfismos Asp299Gly y Thr399Ile no se asocian con la susceptibilidad al SCA en la población mexicana.
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Coronariana Aguda/genética , Polimorfismo de Nucleotídeo Único , /genética , México , Fatores de RiscoRESUMO
Objective: The aim of this study was to test for association between MHC2TA gene polymorphisms and risk for restenosis after coronary stent placement in a group of Mexican patients. Methods: The MHC2TA-168A>G (rs3087456), 1614C>G (rs4774), and 2536G>A (rs2229320) single nucleotide polymorphisms were genotyped using 5' exonuclease TaqMan genotyping assays in a group of 202 patients, who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed, looking for angiographic predictors of restenosis and follow-up angiography was performed to screen for binary restenosis. Results: The results obtained in this study showed that the frequency of the three polymorphisms studied was similar in patients with and without restenosis. Univariate analysis showed that the use of drug-eluting stent (DES) reduces the risk of developing restenosis (p < 0.001, OR = 0.26). In contrast, the diameter< 2.5 mm of the stent and bifurcations increased the risk of developing restenosis (p = 0.049, OR = 1.74 and p = 0.041, OR = 1.8). Conclusion: The present study suggests that the MHC2TA polymorphisms are not involved in the risk of developing restenosis after coronary stent placement.
Objetivo: El propósito de este estudio fue evaluar la asociación de los polimorfismos del gen MHC2TA y el riesgo de desarrollar reestenosis, después del implante de stent coronario en un grupo de pacientes mexicanos. Métodos: Los polimorfismos de un solo nucleótido MHC2TA-168A>G (rs3087456), 1614C>G (rs4774) y 2536G>A (rs2229320), se determinaron en un grupo de 202 pacientes tratados con stent coronario. Los polimorfismos fueron evaluados utilizando ensayos de genotipificacion Taq-Man 5' exonucleasa. El procedimiento basal y la búsqueda de predictores de reestenosis fueron analizados por medio de angiografía coronaria, y seguimiento angiográfico con el fin de detectar reestenosis binaria. Resultados: Los resultados obtenidos en este estudio mostraron que la distribución génica de los tres polimorfismos estudiados fue muy similar, en pacientes con o sin reestenosis. Sin embargo, el análisis univariado mostró que el uso de los stent medicados reducen el riesgo de desarrollar reestenosis (p < 0.001, OR = 0.26). En contraste, con las bifurcaciones y el diámetro < 2.5 mm del stent que se incrementa el riesgo de desarrollar reestenosis (p = 0.049, OR = 1.74 y p = 0.041, OR = 1.8). Conclusión: El presente estudio sugiere que los polimorfismos del gen MHC2TA no están asociados con el riesgo de desarrollar reestenosis, después del implante de stent coronario.
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reestenose Coronária/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Stents , Transativadores/genética , MéxicoRESUMO
La hipertensión arterial es considerada la principal causa de riesgo para el desarrollo de infarto agudo al miocardio, falla cardiaca, arritmia ventricular, nefropatía, ceguera, entre otras. La hipertensión arterial es una enfermedad multifactorial en la que participan factores ambientales, genéticos e intrínsecos como raza y género. La Organización Mundial de la Salud ha estimado que la prevalencia de la hipertensión se incrementará drásticamente, de modo que en la próxima década será la primera causa de muerte a nivel mundial, debido al elevado número de muertes (17.5 millones) por enfermedades cardiovasculares registradas a nivel mundial. No obstante, los datos publicados en la Encuesta Nacional de la Secretaría de Salud en 2006, señalan aproximadamente 17 millones de hipertensos en población adulta y una prevalencia de 30.8%, cifra que indica que la hipertensión arterial aumentó su morbilidad del año 2000 al 2005. Sin embargo, poco se ha logrado en la comprensión de los mecanismos moleculares y genéticos involucrados en el desarrollo de esta patología y en consecuencia su prevalencia sigue aumentando drásticamente. Con el uso de las nuevas tecnologías para el análisis de las variantes en el genoma, se han identificado algunos genes en diferentes loci que confieren susceptibilidad al desarrollo de hipertensión arterial. La finalidad de esta revisión es hacer una comparación entre los diferentes estudios en genética y genómica relacionados con esta patología a nivel mundial y en nuestro país, con la finalidad de identificar genes clave que participen en la susceptibilidad al desarrollo de la hipertensión arterial.
The arterial hypertension is considered to be the main risk factor for myocardial infarction, heart failure, ventricular arrhythmias, kidney failure, blindness and other diseases. Arterial hypertension is a multifactorial disease derived from environmental, genetic, gender and ethnic factors. In recent years, the World Health Organization estimated that approximately 17.5 million of deaths were due to cardiovascular diseases worldwide and that this pathology will become the leading cause of death in the next decade. Data from the National Survey of Mexican Ministry of Health (2006), reported approximately 17 million hypertensive adults, equivalent to a prevalence of 30.8% among Mexican population. As a consequence, hypertension represents the leading cause of morbidity from 2000 to 2005 and is increasing in recent years. However, studies have failed to clearly identify the molecular and genetic mechanisms of this pathology so far. Nevertheless, using the new technologies for analysis of variants in the genome, several genes in different loci that confer susceptibility to develop hypertension have been identified. In this review we compared the different studies in genetics and genomics of the hypertension that have been made worldwide and in Mexico, with the aim of identifying important genes involved in susceptibility to the development of this pathology.
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Humanos , Genômica , Hipertensão/genética , Estudos de Associação Genética , Ligação Genética , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Inflammation plays an important role in the development of atherosclerotic lesions, affecting several stages of the atheroma's development going from the initial leukocyte recruitment to the eventual rupture of the unstable atherosclerotic plaque. The inflammatory reactions within coronary atherosclerotic plaques influence the clinical outcome of acute coronary syndromes and coronary artery disease. Recent studies suggest that inflammation markers may reflect different aspects of the atherothrombotic process in relation to the stages of acute coronary syndrome. These markers play an important role in the risk of developing coronary artery disease, and may correlate with its severity. Some cytokines, acute phase proteins, acute phase reactants proteins, and adhesion molecules released from the inflammatory cells may reflect the inflammatory process in atherosclerotic plaques. However, it remains to be determined whether these pro- and anti-inflammation markers may confer risk or protection for cardiovascular disease, or simply reflect the underlying disease process. The analysis of the markers may be useful for the development of new strategies for coronary disease prevention and treatment. Therefore, we need a well-designed evaluation of these markers before their use in the clinical practice.
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Humanos , Síndrome Coronariana Aguda/sangue , Doença da Artéria Coronariana/sangue , Síndrome Coronariana Aguda/imunologia , Biomarcadores/sangue , Proteína C-Reativa , Moléculas de Adesão Celular/sangue , Quimiocinas/sangue , Doença da Artéria Coronariana/imunologia , Fibrinogênio , Interleucina-1/sangue , /sangue , /sangue , Isquemia Miocárdica/sangue , Isquemia Miocárdica/imunologia , Proteína Amiloide A Sérica , Fator de Crescimento Transformador beta1/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
PURPOSE: To determine the Paraoxonase-1 (PON1) activity as well as its pheno- and genotypes at position 192 in Mexican subjects with diagnosis of coronary heart disease (CHD). METHODS: We determined the PON1-192 polymorphism by PCR-RFLP, and serum PON1 activity, using either paraoxon (PONase activity) or phenylacetate (ARE activity) as substrates, in 155 clinically healthy individuals (control group), and 155 patients with at least one myocardial infarction (CHD group). The biochemical A/B phenotype was determined by the ratio of the NaCI 1 M-stimulated PONase activity divided by the ARE activity. RESULTS: We found significantly lower PONase and ARE activities in CHD patients as compared to controls (233.1 +/- 102.1 vs. 295.8 +/- 159.1 nmol/min/mL, and 103.1 +/- 33.7 vs 220.2 +/- 120.7 micromol/min/mL, respectively, p<0.05 for both). Allele and genotype frequencies for PON1-192 were similar in CHD patients and healthy controls. Moreover, in the control group, the PON1-192 Q/R genotype did not matched with the A/B phenotype as has been proposed by other studies. CONCLUSIONS: There were important differences in the ARE and PONase activities between Mexican CHD patients and controls, suggesting that PON1 activity could be a good marker of CHD risk, whereas PON1-192 lacks of value to assess such risk.
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arildialquilfosfatase , Hidrolases de Éster Carboxílico , Doença da Artéria Coronariana/enzimologia , Arildialquilfosfatase/sangue , Arildialquilfosfatase , Estudos Transversais , Hidrolases de Éster Carboxílico/sangue , Hidrolases de Éster Carboxílico , HDL-Colesterol/sangue , Genótipo , México , Infarto do Miocárdio/enzimologia , Fenótipo , Polimorfismo GenéticoRESUMO
In this work it is emphasized the presence of the fibrinolitico system in different physiological mechanisms, specially in the antithrombotic regulation of the hemostasis. It is described: the mechanism of activation of plasminogen by their activators as much on the fibrin as in the cells surface; the inhibition of the activators in different metabolic alterations.
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Animais , Humanos , Fibrinólise/fisiologia , Hemostasia , TromboseRESUMO
El corazón es el primer órgano que se forma y funciona en el embrión, de tal suerte que todos los eventos subsecuentes en la vida del organismo dependen de la habilidad de este órgano para atender las demandas de oxígeno y nutrientes que éste requiere. Las anormalidades en la formación del corazón, la forma más común de defectos humanos al nacimiento, afecta al 1 % de los nacidos vivos, y su frecuencia en abortos espontáneos se eleva diez veces más. La patofisiología de este tipo de malformaciones congénitas se ha venido enriqueciendo en los últimos años con el conocimiento del Proyecto Genoma Humano; debido al gran avance que se ha producido en el conocimiento genético y molecular de los diferentes genes y cromosomas que suelen ser afectados y muchas veces heredados para producir una enfermedad congénita en general. Esta revisión trata de enfocar su atención sobre la información extraída de los análisis genéticos y moleculares en el diagnóstico, tratamiento y entendimiento de la patogénesis de las enfermedades cardiovasculares pediátricas, dirigidas tanto por los más comunes defectos cardíacos congénitos o heredados, como por los desórdenes esporádicos o adquiridos.
The heart is the first organ to form and function in the embryo, and all subsequent events in the life of the organism depend on the heart's ability to match its output with the organism's demands for oxygen and nutrients. Abnormalities in heart formation, the most common form of human birth defects, afflict nearly 1% of newborns, and their frequency in spontaneously aborted pregnancies is estimated to be tenfold higher. With the completion of the sequencing of the human genome, molecular genetic efforts directed at finding genes for monogenic traits have accelerated dramatically. Breakthroughs in molecular genetic technology have just begun to be applied in pediatric cardiology stemming from the use of chromosomal mapping and the identification of genes involved in both the primary etiology and as significant risk factors in the development of cardiac and vascular abnormalities. This review will focus on information provided by molecular and genetic analysis in the diagnosis, treatment and overall heart disorders.
Assuntos
Humanos , Cardiopatias/congênito , Cardiopatias/genética , Cardiopatias/diagnóstico , Cariotipagem , Biologia Molecular , Técnicas de Diagnóstico MolecularRESUMO
Las lipoproteínas de alta densidad (HDL) son una familia de partículas que difieren en tamaño, densidad y composición química. La heterogeneidad de las HDL resulta de la velocidad de síntesis y de catabolismo de las partículas, y de la acción de enzimas y proteínas de transporte que las remodelan continuamente. Los bajos niveles de colesterol HDL correlacionan con un riesgo elevado de desarrollar enfermedad aterosclerosa coronaria. La disminución de las HDL afecta el transporte reverso de colesterol, que es la vía metabólica responsable de la remoción del colesterol excedente de la células periféricas y su transporte hacia el hígado para reciclarlo o eliminarlo. Las HDL poseen además propiedades antiinflamatorias, antioxidativas, antiagregatorias, anticoagulantes y profibrinolíticas in vitro . Algunas de estas propiedades potencialmente antiaterosclerosas, también se han puesto de manifiesto in vivo con infusiones de HDL. Estas evidencias, además de la protección que se logra en modelos animales genéticamente modificados, permite plantear a las HDL como un objetivo primario en la prevención de la aterosclerosis coronaria. Algunos estudios epidemiológicos han demostrado una reducción importante en el riesgo cardiovascular asociado a elevaciones del colesterol HDL, principalmente en prevención secundaria. En consecuencia, elevar las concentraciones de las HDL a través de medidas higiénicas como el ejercicio aeróbico, la pérdida de peso y eliminar el tabaquismo, es ampliamente recomendado para reducir el riesgo coronario. Cuando las medidas higiénicas fallan, la intervención farmacológica con niacina o fibratos debe ser considerada en ciertos pacientes con niveles bajos de HDL. Por último, las diferentes subclases de HDL no poseen las mismas propiedades antiaterogénicas, lo que sugiere que las intervenciones tanto higiénicas como farmacológicas se deberán enfocar en el futuro hacia incrementos de la funcionalidad de las HDL, más que a incremento en la concentración del colesterol HDL.
High density lipoproteins (HDL) are a family of heterogeneous particles that vary in size, density and chemical composition, as a result of their synthesis and catabolism rates, and a continuous intravascular remodeling by the action of enzymes and transport proteins. Low plasma levels of HDL correlate with a high risk of atherosclerotic heart disease. Such a diminished concentration of HDL affect reverse cholesterol transport, which is the metabolic pathway responsible for the movement of cholesterol excess from peripheral tissues to the liver for recycling or excretion. In addition, HDL possess anti-inflammatory, anti-oxidative, anti-aggregatory, anti-coagulant, and pro-fibrinolytic properties, as has been demonstrated by in vitro studies. Some of those potentially anti-atherosclerotic in vitro-properties has been corroborated by HDL infusion in vivo. Such evidences and the protection of susceptible animals from atherosclerosis by transgenic manipulation of HDL metabolism, raise the possibility to focus the HDL plasma levels as a main target in coronary hearth disease prevention. Intervention trials have shown an important reduction in coronary events by rising HDL-cholesterol, mainly in the secondary prevention. Increasing HDL plasma levels by hygienic intervention such as aerobic exercise, weight loss and stop smoking is strongly recommended to reduce coronary risk in primary prevention. Pharmacological intervention to rise the HDL plasma levels with niacin or fibrates, should be considered in some patients as an alternative when hygienic intervention fails. Finally, it most be taken into account that the different HDL subclasses does not possess the same anti-atherosclerotic properties, suggesting that hygienic and pharmacological interventions should focus to increase HDL functionality rather than HDL-cholesterol plasma levels. (Arch Cardiol Mex 2004; 74:53-67).