Decreased low-density lipoprotein receptor-related protein 1 expression in pro-inflammatory monocytes is associated with subclinical atherosclerosis

Subclinical atherosclerosis (SCA) occurs in asymptomatic individuals. Blood peripheral monocytes are involved in the development of atherosclerosis. Circulating monocytes acquire pro-inflammatory profiles, and they are involved in the early stages of atherosclerosis development. Low-density lipoprotein Receptor-related Protein 1 (LRP1) is expressed in monocytes, mainly in classical and intermediate subsets. Although LRP1 is highly expressed in macrophages and vascular smooth muscle cells (VSMCs) in atherosclerotic plaque formation, its expression in circulating monocytes has not been studied in SCA. The aim of this study was to characterize the LRP1 expression level in circulating monocytes of individuals with SCA and compared with individuals with low (LR) and intermediate (IR) risk of cardiovascular diseases, both without evidence of atherosclerotic lesions in carotid and coronary arteries. LRP1 and additional markers (CD11b, CD11c, and CD36) at cell surface of monocytes were analyzed by flow cytometry assays, whereas LRP1 and pro-inflammatory factors gene expressions were measured in isolated monocytes by quantitative RT-PCRs. Both LRP1 protein and LRP1 mRNA were significantly reduced in monocytes in SCA and IR respect to LR. Conversely, CD36, CD11b, and CD11c monocytic markers showed no significant changes between the different study groups. Finally, increased gene expressions of TNF-α and IL-1β were detected in monocytes of SCA, which were associated with decreased LRP1 expression at the cell surface in total monocytes. In summary, we propose that the decreased LRP1 expression at cell surface in total monocytes with pro-inflammatory profile is associated with the development of atherosclerosis in asymptomatic individuals.Fil: Albertini, Ricardo Arturo. Hospital Privado Centro Medico de Cordoba; ArgentinaFil: Nicolas, Juan C.. Universidad Católica de Córdoba; ArgentinaFil: Actis Dato, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ferrer, Darío G.. Hospital Privado Centro Medico de Cordoba; ArgentinaFil: Tinti, María E.. Hospital Privado Centro Medico de Cordoba; ArgentinaFil: Capra, Raúl H.. Hospital Privado Centro Medico de Cordoba; ArgentinaFil: Chiabrando, Gustavo Alberto. Universidad Nacional de Córdoba; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentin

"Las cajas de herramientas" como instrumento de alfabetización científica

La escuela debe ser generadora de situaciones que favorezcan la interpretación y la resolución de problemas a partir de saberes y habilidades del campo de la ciencia. Alfabetizar científicamente ayuda a los chicos a pensar críticamente y a obtener confianza y seguridad en sus habilidades. Por estas razones y en el marco del proyecto de extensión de interés social 11-54: “Muestra itinerante e interactiva de ciencias” de la Facultad de Ingeniería Química (UNL), nos propusimos diseñar un instrumento que nos permita llevar a las escuelas primarias, de la ciudad de Santa Fe y ciudades aledañas, materiales didácticos que faciliten la enseñanza y el aprendizaje de las ciencias naturales de un modo sistemático y con el rigor científico que corresponde a cada nivel educativo. Con estas cajas los alumnos de escuelas primarias pueden acceder al conocimiento científico a través de la realización de sencillas experiencias de laboratorio, con sustancias de uso en la vida cotidiana y fácil accesibilidad. Para esto se provee de todos los elementos de laboratorio requeridos para tal fin (vaso de precipitados, gradilla, tubos de ensayos, erlenmeyer, embudo, pipeta Pasteur, etc). Además de la provisión de los materiales antes mencionados, la caja contiene una serie de cartillas con orientaciones para el desarrollo de las experiencias. Entre ellas podemos mencionar: el tiempo de duración aproximado de cada una, la lista de materiales, la complejidad de las mismas, la lista de procedimientos, entre otras. Del mismo modo es destacable la formulación de preguntas para contestar antes y después de la experimentación, discutiendo, el saber popular y los resultados obtenidos con los conceptos científicos abordados. También están especificados los pasos para la disposición final y segura de los residuos. Como el éxito de este instrumento de alfabetización depende de múltiples factores que exceden el disciplinar propio, el diseño de las experiencias y su presentación fue realizado atendiendo miradas multidisciplinares. En particular, confluyeron en el mismo físicos, biólogos, bioquímicos, biotecnólogos, sociólogos, comunicadores sociales y diseñadores gráficos. De esta manera, las actividades propuestas están orientadas a la realización de experimentos sencillos, a fin de acercar la ciencia a niños de edad escolar con explicaciones didácticas, fundamentadas científicamente y presentadas con estrategias comunicacionales específicas. Las cajas están siendo presentadas en los distintos establecimientos educativos. Como una actividad previa al trabajo con los alumnos y a los efectos de optimizar el recurso y hacerlo sostenible en el tiempo, se desarrollan jornadas de capacitación de los docentes responsables, obteniéndose hasta el momento respuestas altamente satisfactoria

Decreased low-density lipoprotein receptor-related protein 1 expression in pro-inflammatory monocytes is associated with subclinical atherosclerosis

Subclinical atherosclerosis (SCA) occurs in asymptomatic individuals. Blood peripheral monocytes are involved in the development of atherosclerosis. Circulating monocytes acquire pro-inflammatory profiles, and they are involved in the early stages of atherosclerosis development. Low-density lipoprotein Receptor-related Protein 1 (LRP1) is expressed in monocytes, mainly in classical and intermediate subsets. Although LRP1 is highly expressed in macrophages and vascular smooth muscle cells (VSMCs) in atherosclerotic plaque formation, its expression in circulating monocytes has not been studied in SCA. The aim of this study was to characterize the LRP1 expression level in circulating monocytes of individuals with SCA and compared with individuals with low (LR) and intermediate (IR) risk of cardiovascular diseases, both without evidence of atherosclerotic lesions in carotid and coronary arteries. LRP1 and additional markers (CD11b, CD11c, and CD36) at cell surface of monocytes were analyzed by flow cytometry assays, whereas LRP1 and pro-inflammatory factors gene expressions were measured in isolated monocytes by quantitative RT-PCRs. Both LRP1 protein and LRP1 mRNA were significantly reduced in monocytes in SCA and IR respect to LR. Conversely, CD36, CD11b, and CD11c monocytic markers showed no significant changes between the different study groups. Finally, increased gene expressions of TNF-α and IL-1β were detected in monocytes of SCA, which were associated with decreased LRP1 expression at the cell surface in total monocytes. In summary, we propose that the decreased LRP1 expression at cell surface in total monocytes with pro-inflammatory profile is associated with the development of atherosclerosis in asymptomatic individuals

Association between cardiovascular disease risk scores and subclinical atherosclerosis prevalence in non-elderly adult patients from Argentina

The goal of our study was to use statistical analysis to try to associate cardiovascular disease (CVD) risk scores and the observed prevalence of subclinical atherosclerosis (SA) in a non-elderly adult local population. An observational cross-sectional study was carried out (143 male and 131 female) on non-elderly adults (20?59 years). CVD risk scores included Framingham Risk Scores for 10-year hard (FRS 10 H), 30-year lipid hard or CVD (FRS 30 L H or FRS 30 L CVD), 30 year-body mass index hard or CVD (FRS 30 BMI H or FRS 30 BMI CVD) and Pooled Cohort Risk Equations for either 10 years (PCE 10) or lifetime (PCE LT). The Carotid Ultrasound (CU) study was performed and the Coronary Artery Calcium (CAC) score were obtained to assess SA. The Receiving Operating Characteristic (ROC) curve analysis followed by Youden?s index was used to evaluate and adjust the stratification of CVD risk scores. SA was detected in 32.4% of individuals. The risk scores that showed the biggest areas under the ROC curve were FRS 30 L (H and CVD). When the cut-off values for these CVD risk scores were adjusted, the FRS 30 L H increased the negative predictive value for the low risk group from 87.7 to 97.0% and the FRS 30 L CVD increased the positive predictive values for the high risk group from 69.7 to 85.7%. The CVD risk stratification of non-elderly adults using FRS 30 L H and FRS 30 L CVD may be a useful tool for selecting candidate patients for diagnostic imaging studies that assess their SA prevalence.Fil: Albertini, Ricardo A.. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Hospital Privado Centro Medico de Córdoba; ArgentinaFil: Ferrer, Dario German. Hospital Privado Centro Medico de Córdoba; ArgentinaFil: Romagnoli, Pablo A.. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Tinti, María E.. Hospital Privado Centro Medico de Córdoba; ArgentinaFil: Amigone, José L.. Hospital Privado Centro Medico de Córdoba; ArgentinaFil: Capra, Raúl. Hospital Privado Centro Medico de Córdoba; ArgentinaFil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Decreased low-density lipoprotein receptor-related protein 1 expression in pro-inflammatory monocytes is associated with subclinical atherosclerosis

Subclinical atherosclerosis (SCA) occurs in asymptomatic individuals. Blood peripheral monocytes are involved in the development of atherosclerosis. Circulating monocytes acquire pro-inflammatory profiles, and they are involved in the early stages of atherosclerosis development. Low-density lipoprotein Receptor-related Protein 1 (LRP1) is expressed in monocytes, mainly in classical and intermediate subsets. Although LRP1 is highly expressed in macrophages and vascular smooth muscle cells (VSMCs) in atherosclerotic plaque formation, its expression in circulating monocytes has not been studied in SCA. The aim of this study was to characterize the LRP1 expression level in circulating monocytes of individuals with SCA and compared with individuals with low (LR) and intermediate (IR) risk of cardiovascular diseases, both without evidence of atherosclerotic lesions in carotid and coronary arteries. LRP1 and additional markers (CD11b, CD11c, and CD36) at cell surface of monocytes were analyzed by flow cytometry assays, whereas LRP1 and pro-inflammatory factors gene expressions were measured in isolated monocytes by quantitative RT-PCRs. Both LRP1 protein and LRP1 mRNA were significantly reduced in monocytes in SCA and IR respect to LR. Conversely, CD36, CD11b, and CD11c monocytic markers showed no significant changes between the different study groups. Finally, increased gene expressions of TNF-α and IL-1β were detected in monocytes of SCA, which were associated with decreased LRP1 expression at the cell surface in total monocytes. In summary, we propose that the decreased LRP1 expression at cell surface in total monocytes with pro-inflammatory profile is associated with the development of atherosclerosis in asymptomatic individuals.Fil: Albertini, Ricardo A. Instituto Universitario de Ciencias Biomédicas Córdoba; ArgentinaFil: Nicolas, Juan C. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: Actis Dato, Virginia. Universidad Nacional de Córdoba. CONICET. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI). Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Ferrer, Darío G. Instituto Universitario de Ciencias Biomédicas Córdoba. Hospital Privado Universitario de Córdoba. Servicio de Laboratorios; ArgentinaFil: Tinti, María E. Instituto Universitario de Ciencias Biomédicas Córdoba. Hospital Privado Universitario de Córdoba. Servicio de Diagnóstico por Imágenes; ArgentinaFil: Capra, Raúl H. Instituto Universitario de Ciencias Biomédicas Córdoba. Hospital Privado Universitario de Córdoba. Servicio de Laboratorios; ArgentinaFil: Chiabrando, Gustavo A. Universidad Nacional de Córdoba. CONICET. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI). Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Chiabrando, Gustavo A. Instituto Universitario de Ciencias Biomédicas Córdoba. Centro de Investigación en Medicina Traslacional Severo Amuchástegui (CIMETSA); Argentin

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population