Actividad del Sistema Renina-Angiotensina en relación con sus polimorfismos genéticos

La realización del presente estudio sobre sujetos jóvenes y sanos no hipertensos tiene dos objetivos primordiales: El primero es analizar la relación de los polimorfismos de los genes del Sistema Renina-Angiotensina, el M235T del gen del angiotensinógeno, el Inserción/Delección del gen de la ECA y el A1166C del gen del receptor AT1 para la angiotensina II, con los niveles en plasma de angiotensina I, angiotensina II y angiotensina-(1-7), todas sustancias peptídicas activas del sistema El segundo es relacionar dichos polimorfismos mediante las distintas razones de conversión y correlaciones, de angiotensina I a angiotensina II, de angiotensina I a angiotensina-(1-7), y de angiotensina II a angiotensina-(1-7), con variaciones en la regulación del eje renina-angiotensina. Tras la consecución dicho estudio, no se encontraron diferencias significativas en los niveles de los péptidos de la angiotensina analizados en la población distribuida por genotipos. Los niveles de angiotensina-(1-7), al igual que las razones de conversión A-(1-7)/AI y A-(1-7)/AII, fueron significativamente mayores en varones que en mujeres en sangre circulante. Los polimorfismos influyeron de forma distinta en los valores medios de los péptidos de la angiotensina en hombres y en mujeres, produciendo equilibrios diferentes. Por este motivo deberían ser siempre analizados en relación al sexo

Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure

[Abstract] Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p<0.001) and type-2-diabetes mellitus (OR 4.031, 95%CI 1.099-7.231, p<0.001) were associated as risk factors. The adequate expression of thermogenic genes has been shown as possible protective factors against heart failure with reduced ejection fraction, suggesting that a loss of functional epicardial adipose tissue brown-like features would participate in a deleterious manner on heart metabolism. Thermogenic genes could represent a future novel therapeutic target in heart failure.Ministerio de Salud, Servicios Sociales e Igualdad; PI13/02542Ministerio de Salud, Servicios Sociales e Igualdad; PI11/01661Red de Investigación Cardiovascular (España), RD12/0042/003

ERK5/BMK1 is a novel target of the tumor suppressor VHL: implication in clear cell renal carcinoma

Hi ha quatre pàgines de material suplementari sense numeracióExtracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes

Abstract Background Oxidized low-density lipoproteins and scavenger receptors (SRs) play an important role in the formation and development of atherosclerotic plaques. However, little is known about their presence in epicardial adipose tissue (EAT). The objective of the study was to evaluate the mRNA expression of different SRs in EAT of patients with ischemic heart disease (IHD), stratifying by diabetes status and its association with clinical and biochemical variables. Methods We analyzed the mRNA expression of SRs (LOX-1, MSR1, CXCL16, CD36 and CL-P1) and macrophage markers (CD68, CD11c and CD206) in EAT from 45 patients with IHD (23 with type 2 diabetes mellitus (T2DM) and 22 without T2DM) and 23 controls without IHD or T2DM. Results LOX-1, CL-P1, CD68 and CD11c mRNA expression were significantly higher in diabetic patients with IHD when compared with those without T2DM and control patients. MSR1, CXCL16, CD36 and CD206 showed no significant differences. In IHD patients, LOX-1 (OR 2.9; 95% CI 1.6–6.7; P = 0.019) and CD68 mRNA expression (OR 1.7; 95% CI 0.98–4.5; P = 0.049) were identified as independent risk factors associated with T2DM. Glucose and glycated hemoglobin were also shown to be risk factors. Conclusions SRs mRNA expression is found in EAT. LOX-1 and CD68 and were higher in IHD patients with T2DM and were identified as a cardiovascular risk factor of T2DM. This study suggests the importance of EAT in coronary atherosclerosis among patients with T2DM

Disfunción ventricular sistólica, un nuevo marcador de enfermedad coronaria en pacientes con estenosis aórtica sin infarto de miocardio previo

La determinación de factores clínicos predictivos de la presencia de enfermedad coronaria podría obviar la necesidad de realizar una coronariografía en pacientes seleccionados con estenosis aórtica severa. Se estudió a 315 pacientes (68 ± 8 años) sin infarto previo con estenosis aórtica severa a los que se realizó coronariografía. En el análisis univariable, resultaron significativas la edad (p = 0,001), la dislipemia (p = 0,003), la angina (p = 0,018), el gradiente aórtico (p = 0,001) y la fracción de eyección (FE) reducida (p = 0,006). En el análisis multivariable las variables asociadas de forma independiente a la lesión coronaria fueron la edad (odds ratio [OR] = 1,079, p = 0,01), la FE < 40% (OR = 2,685, p = 0,02), la angina (OR = 2,518, p = 0,04) y la dislipemia (OR = 2,34, p = 0,008). La disfunción ventricular se correlaciona de forma independiente con la presencia de lesiones coronaria

Obstrucción dinámica intraventricular izquierda inducida por esfuerzo

Introducción y objetivos. La obstrucción dinámica intraventricular izquierda puede aparecer ocasionalmente en pacientes sin miocardiopatía hipertrófica. Planteamos si podría aparecer inducida por esfuerzo en pacientes con angina o disnea de esfuerzo sin causa aparente. El objetivo de este estudio prospectivo es conocer: a) si aparece con esfuerzo; b) su incidencia, magnitud y factores determinantes, y c) evolución de los pacientes que la presentan. Pacientes y método. Realizamos ecocardiograma-Doppler basal y postesfuerzo en 211 pacientes con angina o disnea de esfuerzo. Excluimos a los que tenían infarto previo, valvulopatía, disfunción ventricular o hipertrofia ventricular sin hipertensión. Definimos obstrucción dinámica intraventricular como flujo intraventricular con velocidad = 2,5 m/s. Resultados. Se incluyó a 134 pacientes (59 mujeres), con una edad de 58 ± 9 años; el 69,7% tenía antecedentes de hipertensión, el 35%, dislipemia y el 24,6%, diabetes. Apareció obstrucción intraventricular en 18 (13,4%) pacientes, con un gradiente entre 25 y 53 mmHg (media, 32,19 ± 6,6). Las variables demográficas, los factores de riesgo y el ejercicio realizado fueron similares en el grupo A (con obstrucción) y B (sin obstrucción). En el grupo A, ningún paciente tuvo evidencia de isquemia y los 5 que presentaron síntomas durante el esfuerzo tuvieron mayores gradientes (42,65 ± 10,5 frente a 28,15 ± 2,37 mmHg; p < 0,0001) que el resto del grupo A. El análisis multivariante identificó el diámetro del tracto de salida como único factor predictor independiente. Tras un seguimiento de 369,9 ± 133,5 días, no se registraron eventos. Conclusiones. Nuestros datos sugieren que algunos pacientes con angina o disnea de esfuerzo sin evidencia de isquemia pueden tener obstrucción dinámica ventricular izquierda inducida por esfuerzo

Prevalencia de síndrome metabólico según las nuevas recomendaciones de la OMS: Estudio HERMEX Prevalence of metabolic syndrome estimated with the new World Health Organization recommendations: The HERMEX study

Objetivos: La unificación de criterios para el diagnóstico del síndrome metabólico, junto con la propuesta de la Organización Mundial de la Salud de eliminar de ellos a los pacientes con diabetes o con enfermedades cardiovasculares, cambiará la estimación de su prevalencia. Nuestro objetivo fue determinar la prevalencia del síndrome metabólico en un área de salud extremeña siguiendo ambas recomendaciones. Métodos: Estudio transversal, poblacional, con selección aleatoria de individuos entre 25 y 79 años de edad, en un Área de Salud de Badajoz. Se recogieron los antecedentes de factores de riesgo cardiovascular, la presión arterial y el perímetro abdominal, y una muestra de sangre en ayunas. Se comparó la prevalencia del síndrome metabólico siguiendo los recientes criterios, por sexo y edad. Resultados: Se reclutaron 2.833 personas, el 46,5% eran hombres, y la edad media 51,2 años. La prevalencia del síndrome metabólico fue del 33,6%, significativamente mayor en los hombres (36,7% frente a 30,9%; pObjectives: The unification of criteria for the diagnosis of metabolic syndrome, together with the subsequent World Health Organization (WHO) proposal to eliminate diabetes and cardiovascular diseases from the diagnostic criteria, will change estimates of the known prevalence of this syndrome. The aim of this study was to determine the prevalence of metabolic syndrome in a health area of Badajoz (Spain) using the latest consensus criteria and eliminating diabetes and cardiovascular disease. Methods: We performed a cross-sectional population-wide study of randomly selected individuals aged between 25 and 79 years old in a health area of Badajoz. In all patients, data on their history of cardiovascular risk factors were gathered, waist circumference and blood pressure were measured and a fasting blood sample was collected. The prevalence of metabolic syndrome, following recent criteria, was compared by age and gender. Results: We recruited 2,833 individuals (46.5% men). The mean age was 51.2 years The prevalence of metabolic syndrome was 33.6% and was significantly higher in men (36.7% vs 30.9%; p<0.001). The prevalence of metabolic syndrome fell significantly after exclusion of patients with diabetes or cardiovascular disease (20.8%; p<0.001). The difference in prevalence between the distinct criteria was significant for the whole population and by sex (p<0.000). A significant difference in prevalence between genders was observed from the age of 45-54 years in men and 55-64 years in women. Conclusions: The prevalence of metabolic syndrome in a health area of Badajoz is among the highest reported in population-based studies in Spain. Although estimates of the prevalence are decreased by the new international recommendations, a considerable proportion of the young population requires preventive measures