Increasing the complexity of lipoprotein characterization for cardiovascular risk in type 2 diabetes.

The burden of cardiovascular disease is particularly high among individuals with diabetes, even when LDL cholesterol is normal or within the therapeutic target. Despite this, cholesterol accumulates in their arteries, in part, due to persistent atherogenic dyslipidaemia characterized by elevated triglycerides, remnant cholesterol, smaller LDL particles and reduced HDL cholesterol. The causal link between dyslipidaemia and atherosclerosis in T2DM is complex, and our contention is that a deeper understanding of lipoprotein composition and functionality, the vehicle that delivers cholesterol to the artery, will provide insight for improving our understanding of the hidden cardiovascular risk of diabetes. This narrative review covers three levels of complexity in lipoprotein characterization: 1-the information provided by routine clinical biochemistry, 2-advanced nuclear magnetic resonance (NMR)-based lipoprotein profiling and 3-the identification of minor components or physical properties of lipoproteins that can help explain arterial accumulation in individuals with normal LDLc levels, which is typically the case in individuals with T2DM. This document highlights the importance of incorporating these three layers of lipoprotein-related information into population-based studies on ASCVD in T2DM. Such an attempt should inevitably run in parallel with biotechnological solutions that allow large-scale determination of these sets of methodologically diverse parameters.

Lipidomics Reveals Myocardial Lipid Composition in a Murine Model of Insulin Resistance Induced by a High-Fat Diet.

Ectopic fat accumulation in non-adipose tissues is closely related to diabetes-related myocardial dysfunction. Nevertheless, the complete picture of the lipid metabolites involved in the metabolic-related myocardial alterations is not fully characterized. The aim of this study was to characterize the specific lipid profile in hearts in an animal model of obesity/insulin resistance induced by a high-fat diet (HFD). The cardiac lipidome profiles were assessed via liquid chromatography-mass spectrometry (LC-MS)/MS-MS and laser desorption/ionization-mass spectrometry (LDI-MS) tissue imaging in hearts from C57BL/6J mice fed with an HFD or standard-diet (STD) for 12 weeks. Targeted lipidome analysis identified a total of 63 lipids (i.e., 48 triacylglycerols (TG), 5 diacylglycerols (DG), 1 sphingomyelin (SM), 3 phosphatidylcholines (PC), 1 DihydroPC, and 5 carnitines) modified in hearts from HFD-fed mice compared to animals fed with STD. Whereas most of the TG were up-regulated in hearts from animals fed with an HFD, most of the carnitines were down-regulated, thereby suggesting a reduction in the mitochondrial ß-oxidation. Roughly 30% of the identified metabolites were oxidated, pointing to an increase in lipid peroxidation. Cardiac lipidome was associated with a specific biochemical profile and a specific liver TG pattern. Overall, our study reveals a specific cardiac lipid fingerprint associated with metabolic alterations induced by HFD.

The Lipoprotein Profile Evaluated by 1H-NMR Improves the Performance of Genetic Testing in Familial Hypercholesterolemia.

BACKGROUND: The familial hypercholesterolemia (FH) diagnosis is based on clinical and genetic criteria. A relevant proportion of FH patients fulfilling the criteria for definite FH have negative genetic testing. Increasing the identification of true genetic-based FH is a clinical challenge. Deepening the analysis of lipoprotein alterations could help increase the yield of genetic testing. We evaluated whether the number, size, and composition of lipoproteins assessed by 1H-NMR could increase the identification of FH patients with pathogenic gene variants. METHODS: We studied 294 clinically definite FH patients, 222 (75.5%) with positive genetic testing, as the discovery cohort. As an external validation cohort, we studied 88 children with FH, 72 (81%) with positive genetic testing. The advanced lipoprotein test based on 1H-NMR (Liposcale®) was performed at baseline after a lipid-lowering drug wash-out of at least 6 weeks. The association of variables with genetic variants was evaluated by random forest and logistic regression. Areas under the curve (AUCs) were calculated. A predictive formula was developed and applied to the validation cohort. RESULTS: A formula derived from NMR lipoprotein analyses improved the identification of genetically positive FH patients beyond LDL-C levels (AUC=0.87). The parameters contributing the most to the identification formula were LDL particle number, HDL size and remnant cholesterol. The formula also increases the classification of FH children with a pathogenic genetic variation. CONCLUSIONS: NMR lipoprotein profile analysis identifies differences beyond standard lipid parameters that help identify FH with a positive pathogenic gene variant, increasing the yield of genetic testing in FH patients.

Niveles plasmáticos de glucosa, triglicéridos, VLDL, leptina y resistina como potenciales biomarcadores de la grasa miocárdica en ratones / Plasma glucose, triglycerides, VLDL, leptin and resistin levels as potential biomarkers for myocardial fat in mice

Introducción: El incremento de grasa miocárdica ha sido propuesto como uno de los principales precursores de la disfunción miocárdica de etiología diabética independiente de la enfermedad arterial coronaria. Sin embargo, actualmente se carece de biomarcadores que reflejen el contenido de grasa miocárdica para la detección clínica de esta patología. Métodos: Las correlaciones entre el contenido de triglicéridos cardíacos y los niveles plasmáticos de las principales moléculas alteradas durante la diabetes y los niveles cardíacos de ARNm de genes implicados en el metabolismo cardíaco (Cd36 y Pdk4) han sido exploradas en un modelo murino de resistencia a la insulina inducida por una dieta con alto contenido en grasas. Resultados: En ratones resistentes a la insulina, la dieta grasa aumentó los niveles de triglicéridos del miocardio, en comparación con animales controles alimentados con una dieta estándar. El contenido de triglicéridos cardíacos se encontró directamente asociado con los niveles plasmáticos de glucosa, triglicéridos, VLDL, resistina y leptina. Además, se observó una correlación inversa entre el contenido de triglicéridos y los niveles cardíacos de ARNm de Cd36 y Pdk4. Conclusiones: Nuestros datos revelan que el contenido cardíaco de triglicéridos se encuentra asociado con un perfil bioquímico plasmático alterado y con una reprogramación de la expresión de genes dirigida a atenuar el impacto de la acumulación ectópica de lípidos en miocardio

Introduction: The increase in myocardial fat has been proposed as one of the main precursors of myocardial dysfunction due to diabetic aetiology, independently of coronary artery disease. However, biomarkers reflecting the myocardial fat content for the clinical detection of this pathology are currently lacking. Methods: Correlations between 4cardiac triglyceride content and plasma levels of major altered molecules during diabetes and cardiac mRNA levels of genes involved in cardiac metabolism (Cd36 and Pdk4) have been explored in a murine model of insulin resistance induced by a high-fat diet. Results: In insulin-resistant mice, the fatty diet increased myocardial triglyceride levels, compared to control animals fed with a standard diet. The content of cardiac triglycerides was directly associated with plasma levels of glucose, triglycerides, VLDL, resistin and leptin. In addition, an inverse correlation was observed between the content of cardiac triglycerides and the cardiac mRNA levels of Cd36 and Pdk4. Conclusions: Our data reveal that the cardiac triglyceride content is associated with altered plasma biochemical profile and reprogramming of gene expression aimed to mitigate the impact of ectopic lipid accumulation in the myocardium

Efficacy of therapeutic lifestyle changes on lipid profiles assessed by NMR in children with familial and non-familial hypercholesterolemia / Eficacia de los cambios terapéuticos en el estilo de vida en el perfil lipídico evaluado por RMN en niños con hipercolesterolemia familiar y no familiar

Background and aims: The first line of therapy in children with hypercholesterolaemia is therapeutic lifestyle changes (TLSC). The efficacy of lifestyle intervention in children with familial hypercholesterolaemia (FH), where LDL-C levels are genetically driven, deserves a focused study. Aims: To evaluate the impact of a lifestyle education program, focused on food patterns and physical activity, on lipid profiles assessed by nuclear magnetic resonance (NMR) in children with FH vs. non-FH. Methods: Phase 1 was a cross-sectional study of baseline characteristics, and phase 2 was a prospective TLSC intervention study. In total, the study included 238 children (4 to 18 years old; 47% girls) attending the lipid unit of our hospital due to high cholesterol levels. Eighty-five were diagnosed with FH (72% genetic positive), and 153 were diagnosed with non-Familial hypercholesterolaemia. A quantitative food frequency questionnaire (FFQ) including 137 items was used. Physical activity (PA) was assessed by the Minnesota questionnaire. The lipid profile was assessed using the 2D-1H-NMR (Liposcale test). A total of 127 children (81 in the FH group) participated in the prospective phase and were re-assessed after 1 year of the TLSC intervention, consisting of education on lifestyle changes delivered by a specialized nutritionist. Results: The FH and non-FH groups were similar in anthropometry and clinical data, except that those in the FH were slightly younger than those in the non-FH group. Both the FH and non-FH groups showed a similar diet composition characterized by a high absolute calorie intake and a high percentage of fat, mainly saturated fat. The PA was below the recommended level in both groups. After one year of TLSC, the percentage of total and saturated fats was reduced, and the amount of fiber increased significantly in both groups. The percentage of protein increased slightly. The number of children engaged in at least 1 hour/day of PA increased by 56% in the FH group and by 53% in the non-FH group, and both these increases were significant. The total and small-LDL particle numbers were reduced in both groups, although the absolute change was greater in the FH group than in the non-FH group. Conclusions: Educational strategies to implement TLSC in children lead to empowerment, increased adherence, and overall metabolic improvement in children with high blood cholesterol, including those with FH

Antecedentes y objetivos: La primera línea de terapia en niños con hipercolesterolemia son los cambios terapéuticos en el estilo de vida (TLSC). La eficacia de la intervención en el estilo de vida en niños con hipercolesterolemia familiar (HF), en los que los niveles de LDL-C son generados genéticamente, merece un estudio específico. Objetivos: Evaluar el impacto de un programa de educación sobre el estilo de vida, centrado en los patrones alimentarios y la actividad física, sobre el perfil lipídico evaluado por resonancia magnética nuclear (RMN) en niños con HF versus no HF. Métodos: La fase 1 fue un estudio transversal de las características basales, y la fase 2 fue un estudio prospectivo de intervención mediante TLSC. En total, el estudio incluyó a 238 niños (de 4 a 18 años; 47% niñas) que asistieron a la unidad de lípidos de nuestro hospital debido a los altos niveles de colesterol. Ochenta y cinco fueron diagnosticados con HF (72% genéticamente positivos), y 153 fueron diagnosticados de no HF. Se utilizó un cuestionario cuantitativo de frecuencia de alimentos (FFQ) que incluye 137 ítems. La actividad física (AF) se evaluó mediante el cuestionario de Minnesota. El perfil lipídico se evaluó mediante la prueba 2D-1H-NMR (Liposcale Test). Un total de 127 niños (81 en el grupo HF) participaron en la fase prospectiva y fueron reevaluados después de 1 año de la intervención mediante TLSC, que consistió en educación sobre cambios en el estilo de vida impartida por una nutricionista especializada. Resultados: Los grupos HF y no HF fueron similares en los datos antropométricos y clínicos, excepto que los HF eran ligeramente más jóvenes que los no HF. Los participantes de ambos grupos mostraron una composición de dieta similar caracterizada por un alto consumo de calorías totales y un alto porcentaje de grasas, principalmente grasas saturadas. La AF estuvo por debajo del nivel recomendado en ambos grupos. Después de un año de TLSC, se redujo el porcentaje de grasas totales y saturadas, y la cantidad de fibra aumentó significativamente en ambos grupos. El porcentaje de proteína aumentó ligeramente. El número de niños involucrados en al menos 1 hora/día de AF aumentó en un 56% en el grupo de HF y en un 53% en el grupo sin HF, y ambos aumentos fueron significativos. Los números de partículas LDL totales y pequeñas se redujeron en ambos grupos, aunque el cambio absoluto fue mayor en el grupo HF que en el grupo no HF. Conclusiones: Las estrategias educativas para implementar TLSC en niños conducen al empoderamiento, al aumento de la adherencia y a la mejora metabólica general en niños con colesterol alto en sangre, incluidos aquellos con HF

Efecto a largo plazo del tratamiento con presión positiva continua de la vía aérea sobre la arteriosclerosis subclínica en el síndrome de apnea-hipopnea durante el sueño / Long-term effects of continuous positive airway pressure treatment on subclinical atherosclerosis in obstructive sleep apnoea syndrome

Antecedentes y objetivo: El síndrome de apnea-hipopnea durante el sueño (SAHS) es un factor de riesgo de arteriosclerosis. Nuestro objetivo fue evaluar la arteriosclerosis subclínica en los pacientes con SAHS y el efecto del tratamiento con continuous positive airway pressure (CPAP, «presión positiva continua de la vía aérea superior») sobre el grosor íntima-media carotídeo (GIMc). Pacientes y método: Se incluyeron 125 pacientes con sospecha de SAHS. Después de la polisomnografía, 107 pacientes fueron diagnosticados de SAHS; 58 cumplían criterios de tratamiento con CPAP. El GIMc se midió mediante ecografía a nivel basal y a los 2 años de seguimiento en 50 pacientes con SAHS en tratamiento con CPAP y 35 SAHS sin criterio de CPAP. Resultados: Los valores del GIMc fueron superiores en los pacientes con SAHS respecto a los que no tenían SAHS (665 ± 120 frente a 581 ± 78 μm, p = 0,005), sin asociarse con su nivel de gravedad. La presencia de placas de ateroma fue más prevalente en los SAHS que en los no SAHS (48 frente a 2%, p = 0,004). En los pacientes con SAHS, la media del GIMc permaneció estable durante el seguimiento en el grupo sin CPAP, y en el grupo tratado con CPAP disminuyó significativamente (679 ± 122 frente a 631 ± 117 μm, p < 0,0001). Conclusiones: Los pacientes con SAHS presentan un mayor grado de arteriosclerosis subclínica y no se asocia con su gravedad. La ecografía carotídea en el SAHS es un marcador fiable de arteriosclerosis. El tratamiento con CPAP en el SAHS disminuye el GIMc y el riesgo cardiovascular (AU)

Background and objective: Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease. Our objective was to evaluate subclinical atherosclerosis in OSA patients and the effect of continuous positive airway pressure (CPAP) treatment on carotid intima-media thickness (cIMT). Patients and method: We included 125 patients with suspected OSA. After polysomnography, 107 patients were diagnosed with OSA; 58 of these met the criteria for CPAP treatment. cIMT was measured by ultrasonography at baseline in all patients and after 2 years of follow up in 50 patients on CPAP and 35 without CPAP treatment. ResultsThe average cIMT was significantly thicker in OSA than in non-OSA patients (665 ± 120 vs. 581 ± 78 μm, P = .005) and did not differ according to OSA severity. Atheromatous carotid plaque was more prevalent in OSA than non-OSA patients (48 vs. 2%, P = .004). Among OSA patients, the mean cIMT remained stable over time in the group without CPAP, whereas cIMT decreased markedly in the CPAP group (679 ± 122 vs. 631 ± 117 μm, P < .0001). Conclusions: Increased cIMT was associated with presence of OSA, but not with its severity. Carotid ultrasound in OSA is a reliable marker of atherosclerosis. CPAP treatment with CPAP in OSA reduces cIMT and cardiovascular risk (AU)

Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders / Concentraciones circulantes de PCSK9 en población con diabetes tipo 2 y alteraciones metabólicas asociadas

Background: PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis. Methods: There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients. Results: The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%;p < 0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C). Conclusions: PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism

Introducción: PCSK9 es una molécula clave en la regulación del metabolismo lipídico. Estudios previos sugieren que la expresión y función de PCSK9 entorno a la regulación del receptor LDL puede alterarse en la diabetes. El objetivo del estudio fue determinar los niveles circulantes de PCSK9 en pacientes con diabetes tipo 2 (DM) y otras enfermedades metabólicas y su relación con las lipoproteínas estudiadas mediante resonancia magnética nuclear (RMN) y la homeostasis de la glucosa. Métodos: Se estudiaron un total de 457 pacientes, afectos de DM y otras alteraciones metabólicas (síndrome metabólico [SMet], obesidad y dislipidemia aterogénica [DA] y otros). Se realizó anamnesis, antropometría, exploración física y estudio vascular de carótidas y adiposidad abdominal. Se realizó bioquímica incluyendo PCSK9 circulante (tras 6 semanas de lavado en pacientes con hipolipemiantes). Se estudió mediante RMN el perfil de lipoproteínas. Se determinaron las variantes genéticas rs505151 y rs11591147 del gen PCSK9. Resultados: Los niveles circulantes de PCSK9 están aumentados en pacientes con DM y SMet (14 y 13%; p<0.005, respectivamente). Los niveles circulantes de PCSK9 se correlacionaron de forma positiva con el perfil lipídico aterogénico y parámetros de resistencia insulínica. Los niveles circulantes de PCSK9 también se asociaron positivamente a DA, definida mediante el número y el tamaño de lipoproteínas analizado mediante RMN. Los portadores de la variante genética rs11591147 mostraron niveles inferiores de PCSK9 plasmática y cLDL. Conclusiones: Los niveles circulantes de PCSK9 están aumentados en pacientes con DM y SMet junto con parámetros de DA y metabolismo de la glucosa, más allá del cLDL

Interacción de FABP4 con proteínas de membrana de células endoteliales / Interaction of FABP4 with plasma membrane proteins of endothelial cells

Introducción: Fatty acid-binding protein 4 (FABP4) es una adipocina secretada por el tejido adiposo implicada en la regulación del metabolismo energético y la inflamación. FABP4 circulante se asocia con obesidad, dislipidemia aterogénica y síndrome metabólico. Estudios recientes muestran una asociación entre FABP4 circulante y disfunción endotelial, aunque se desconoce cómo se produce esta. El objetivo de este trabajo es estudiar la interacción entre FABP4 con las proteínas de la membrana citoplasmática en células endoteliales. Metodología: Se incubaron células HUVEC con y sin FABP4 (100 ng/ml) durante 5 min. La inmunolocalización de FABP4 se estudió mediante microscopia confocal. Para estudiar las interacciones de FABP4 con las proteínas de membrana de las células HUVEC se diseñó una estrategia que combina incubaciones con o sin 6XHistidine-tag FABP4 (FABP4-His) (100 ng/ml), cross-linking con formaldehído, extracción de proteínas de membrana y western blot. Resultados: Los resultados muestran que FABP4 colocaliza con CD31, una proteína utilizada como marcador de membrana citoplasmática. Además se observan diferentes patrones de western blot en función de la incubación con o sin FABP4-His. El inmunoblot revela la existencia de 3 complejos proteicos de aproximadamente 108, 77 y 33 kDa formados por FABP4 exógena y su posible receptor/es. Discusión: Los resultados obtenidos apoyan la existencia de un complejo proteico capaz de unir FABP4 a las células endoteliales mediante una unión específica. Además, nos permiten avanzar en el conocimiento de los efectos moleculares de FABP4 y, en caso de confirmarse, podrían utilizarse como diana terapéutica para prevenir enfermedades cardiovasculares

Introduction: Fatty acid binding protein (FABP4) is an adipose tissue-secreted adipokine implicated in the regulation of the energetic metabolism and inflammation. High levels of circulating FABP4 have been described in people with obesity, atherogenic dyslipidemia, diabetes and metabolic syndrome. Recent studies have demonstrated that FABP4 could have a direct effect on peripheral tissues and, specifically, on vascular function. It is still unknown how the interaction between FABP4 and the endothelial cells is produced to prompt these effects on vascular function. The objective of this work is studying the interaction between FABP4 and the plasma membrane proteins of endothelial cells. Methodology: HUVEC cells were incubated with and without FABP4 (100 ng/ml) for 5 minutes. Immunolocalization of FABP4 was studied by confocal microscopy. The results showed that FABP4 colocalizates with CD31, a membrane protein marker. A strategy which combines 6XHistidine-tag FABP4 (FABP4-His), incubations with or without FABP4-His (100 ng/ml), formaldehyde cross-linking, cellular membrane protein extraction and western blot, was designed to study the FABP4 interactions with membrane proteins of HUVECs. Results: The results showed different western blot profiles depending of the incubation with or without FABP4-His. The immunoblot revelead three covalent protein complexes of about 108, 77 and 33 kDa containing FAPB4 and its putative receptor. Discussion: The existence of a specific binding protein complex able to bind FABP4 to endothelial cells is supported by these results. The obtained results will permit us advance in the molecular knowledge of FABP4 effects as well as use this protein and its receptor as therapeutic target to prevent cardiovascular

Low-carbohydrate, high-protein, high-fat diet alters small peripheral artery reactivity in metabolic syndrome patients

Background: Low carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or metabolic syndrome (MS), their net effect on vascular function remains unclear. Objective Evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery vascular function, in a cohort of MS patients. Design This cross-sectional study included 160 MS patients. Diet was evaluated by a 3-day food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and saRHI was measured in each patient. Results Individuals in the lowest LCDS quartile (Q1; 45% carbohydrate, 19% protein, 31% fat) had higher saRHI values than those in the top quartile (Q4; 30% carbohydrate, 25% protein, 43% fat) (1.84 ± 0.42 vs. 1.55 ± 0.25, P = .012). These results were similar in T2D patients (Q1 = 1.779 ± 0.311 vs. Q4 = 1.618 ± 0.352, P = .011) and also in all of the MS components, except for low HDLc. Multivariate analysis demonstrated that individuals in the highest LCDS quartile, that is, consuming less carbohydrates, had a significantly negative coefficient of saRHI which was independent of confounders (HR: -0.747; 95%CI: 0.201, 0.882; P = .029). Conclusions These data suggest that a dietary pattern characterized by a low amount of carbohydrate, but reciprocally higher amounts of fat and protein, is associated with poorer vascular reactivity in patients with MS and T2D

Introducción: Las dietas bajas en hidratos de carbono son muy populares para la pérdida de peso. Aunque estas puedan mejorar algunos marcadores metabólicos, en particular en la diabetes mellitus tipo 2 (DM2) o en el síndrome metabólico (SM), su efecto neto sobre la función de la pared arterial sigue siendo poco clara. Objetivo: Evaluar la relación entre la composición de macronutrientes de la dieta y el índice de hiperemia reactiva de pequeña arteria (saRHI) en una cohorte de pacientes con SM. Diseño: En este estudio transversal se incluyeron 160 pacientes con SM. La dieta fue evaluada mediante un registro alimentario de 3 días que se tradujo a una puntuación de dieta baja en hidratos de carbono (LCDS). Se registraron los parámetros demográficos, bioquímicos, antropométricos, y el saRHI se determinó en cada paciente. Resultados: Los individuos en el cuartil inferior de LCDS (C1, 45% de hidratos de carbono, 19%de proteína y 31% grasa) presentaron valores más altos de saRHI en comparación a con delcuartil superior (C4, 30% de hidratos de carbono, 25% de proteínas, 43% de grasa) (1,84±0,42vs. 1,55±0,25, p= ,012). Estos resultados fueron particularmente semejantes en los pacientes con DM2 (C1 = 1,779±0,311 vs. C4 = 1,618±0,352, p= ,011) y en todos los componentes del SM, excepto por los niveles bajos de cHDL. En el análisis multivariante se observó que los individuos en el cuartil superior del LCDS consumían menos hidratos de carbono, tenían un coeficiente negativo de saRHI alto independiente de los factores de confusión (HR: -0,747; IC95%: 0,201, 0,882; p = ,029). Conclusiones Estos hallazgos sugieren que un patrón alimentario caracterizado por una baja cantidad de hidratos de carbono, pero altas cantidades de proteínas y grasas, se asocia con una menor reactividad vascular de arteria pequeña en pacientes con SM

La depleción de células CD34 +/CD144+ en pacientes de revascularización miocárdica no está mediada por un aumento de la apoptosis inducida por el TGF-beta plasmático / CD34 +/CD144+ cell depletion in coronary artery bypass patients is not related to increased apoptosis by plasmatic TGF-beta

Introducción La arteriosclerosis coronaria se ha relacionado con la depleción y la alteración funcional de las células progenitoras endoteliales (EPC). Nos propusimos determinar el número de células CD34+/KDR+ y CD34+/CD144+ en pacientes sometidos a revascularización miocárdica quirúrgica, comparados con pacientes operados de recambio valvular, así como el efecto de su plasma sobre EPC cultivadas de donantes sanos. Métodos El número de CD34+/KDR+ y CD34+/CD144+ se determinó por citometría de flujo. Las EPC cultivadas se obtuvieron de residuos leucoplaquetarios transfusionales. La apoptosis se midió por fragmentación de ADN. La expresión de CD34 y CD144 se determinó por Western blot. Resultados Encontramos un menor número de CD34+/CD144+ en pacientes revascularizados comparados con los de recambio valvular, pero en ambos casos fue un número mayor que el hallado en sujetos sanos. El plasma de pacientes revascularizados tuvo un efecto antiapoptótico sobre EPC de sujetos sanos (al día 7 de aislamiento), y este efecto fue inhibido por los bloqueadores de la vía del TGF-beta1 SIS3 y SB-431542. Previo a ello, en el día 4, el plasma de los pacientes revascularizados aumentó la expresión in vitro de CD34 y CD1144.Conclusión El plasma de los pacientes revascularizados es antiapoptótico y aumenta la expresión de CD34 y CD144 en EPC de donantes sanos. Por lo tanto, el número subóptimo de CD34+/CD144+ que se observa in vivo sugiere un defecto en su liberación de la médula ósea (AU)

Introduction Coronary atherosclerotic disease has been linked to endothelial progenitor cell (EPC) depletion and functional impairment. We assessed the number of CD34+/KDR+ and CD34+/CD144+ cells in coronary artery bypass grafting (CABG) patients, compared to valvular patients, and the apoptotic effect of the plasma from these two groups on early outgrowth cells (EOCs) from healthy donors. Methods CD34+/KDR+ and CD34+/CD144+ cell numbers were assessed by flow cytometry. EOCs were obtained from buffy coats from healthy donors. Apoptosis was measured as DNA fragmentation. In vitro expression of CD34 and CD144 was assessed by Western blot. Results We found a lower number of CD34+/CD144+ cells in CABG patients compared to valvular, but a higher number compared to healthy controls. Plasma from CABG patients decreased apoptosis in cultured EOCs from healthy donors (day 7); this effect was abrogated by the TGF-beta1 blockers SIS3 and SB-431542. Prior to apoptosis protection, in cultured cells from healthy donors (day 4), plasma from CABG increased CD34 and CD144 expression, contrary to what found in the blood of the patients. Conclusions CABG patients possess a lower number of CD34+/CD144+ cells than valvular ones. Plasma from CABG patients is antiapoptotic for EOCs from healthy donors and increases the expression of both CD34 and CD144. Suboptimal number of CD34+/CD144+ in vivo may be mediated by a primary bone marrow defect rather than a deleterious effect of plasma(AU)

Las concentraciones de Apo-B100 en los pacientes con hipercolesterolemia familiar se asocian a una mayor rigidez arterial / Apolipoprotein-B100 concentrations are associated with increased arterial stiffness in familial hypercholesterolemia

Introducción: La hipercolesterolemia familiar (HF) heterocigota es un trastorno genético del metabolismo de las lipoproteinas que conlleva un riesgo cardiovascular (RCV) muy elevado. El estudio de la pared arterial y su función son de especial interés en pacientes con HF. La rigidez arterial está asociada a un incremento del RCV. El objetivo del estudio fue determinar la rigidez arterial en pacientes con HF y su asociación con parámetros bioquímicos y vasculares. Métodos (..) (AU)

Introduction: Familial hypercholesterolemia (FH) is a genetic disease of lipoprotein metabolism conferring a high cardiovascular risk (CVR) to patients. Arterial wall properties and function study are of interest in FH subjects. Arterial stiffness is associated with a higher CVR. The aim of our study was to determine the arterial stiffness in FH patients and its association with vascular and biochemical parameters. Methods: One hundred and twenty-five FH subjects and 59 healthy volunteers were included. Clinical, anthropometrical and biochemical data were collected. Vascular studies were performed by measuring the augmentation index adjusted for 75 beats per minute of heart rate(AIx@75) as an arterial stiffness marker by peripheral artery tonometry, the carotid intimamedia thickness (cIMT) by ultrasonography and the brachial-ankle index (ABI).Results: FH patients showed a significant increase in the AIx@75 respect to control group (CG)(9,8 ± 18,3 vs 2,4 ± 111,1%; p = 0,001), and higher cIMT (0,758 ± 0,280 vs 0,635 ± 0,160 mm;p < 0,001). We did not observe differences in ABI between groups. The AIx@75 values were directly correlated with LDL cholesterol, Apolipoprotein-B100 (Apo-B 100), triglycerides and sE-selectin. Apo-B100, systolic blood pressure and fasting glucose were the main determinants of the AIx@75. AIx@75 was also an independent predictor of cIMT. Conclusions: FH patients have increased arterial stiffness. The AIx@75 is clearly associated withApo-B100 concentrations and it is a cIMT determinant. The AIx@75 may be an early marker of CVR in FH subjects (AU)

FABP4, función endotelial y grosor de la íntima-media carotídeoen pacientes con riesgo cardiovascular / FABP4, endothelial function and carotid intima-media thickness in cardiovascular risk patients

Introducción: Los niveles plasmáticos de la proteína FABP4 son superiores en pacientes con diabetes tipo 2 (DT2), obesidad y síndrome metabólico. La disfunción endotelial es una característica común en el desarrollo de las enfermedades vasculares asociadas a las alteraciones metabólicas. El objetivo del trabajo es estudiar la relación entre FABP4 circulante y la función endotelial en pacientes con elevado riesgo cardiovascular (RCV).Métodos: Doscientos cincuenta y siete pacientes (57,29±10,66 años) con RCV incrementado. Se determinó FABP4 plasmática. En el estudio vascular se valoró la función endotelial mediante el índice de la hiperemia reactiva (IHR) por tonometría arterial periférica, el grosor de la (..) (AU)

Objective: Adipocyte fatty acid binding protein (FABP4) plasma levels are higher in type 2 diabetes(T2D), obesity and metabolic syndrome. Endothelial dysfunction is a common feature in the development of vascular diseases associated with metabolic disturbances. We have investigated the relationship between circulating FABP4 levels and endothelial function in patients at cardiovascular risk. Methods: Two hundred and fifty-seven patients (mean age, 57.29±10.66 years) at increased cardiovascular risk (CVR). Fasting plasma FABP4 levels were measured. Endothelial function was assessed as reactive hyperemia (IHR) by peripheral artery (..) (AU)