Markers of inflammation and cardiovascular disease in recently diagnosed celiac disease patients

AIM: To evaluate novel risk factors and biomarkers of cardiovascular disease in celiac disease (CD) patients compared with healthy controls.METHODS:Twenty adult patients with recent diagnosis of CD and 20 sex, age and body mass index-matched healthy controls were recruited during a period of 12 mo.Indicators of carbohydrate metabolism, hematological parameters and high sensitive C reactive protein were determined. Moreover, lipoprotein metabolism was also explored through evaluation of the lipid profile and the activity of cholesteryl ester transfer protein and lipoprotein associated phospholipase A2, which is also considered a specific marker of vascular inflammation. The protocol was approved by the Ethic Committee from School of Pharmacy and Biochemistry, University of Buenos Aires and from Buenos Aires Italian Hospital, Buenos Aires, Argentina.RESULTS: Regarding the indicators of insulin resistance, CD patients showed higher plasma insulin levels [7.2 (5.0-11.3) mU/L vs 4.6 (2.6-6.7) mU/L, P < 0.05], increased Homeostasis Model Assessment-Insulin Resistance [1.45 (1.04-2.24) vs 1.00 (0.51-1.45), P < 0.05] and lower Quantitative Sensitive Check index [0.33 (0.28-0.40) vs 0.42 (0.34-0.65), P < 0.05] indexes. Folic acid concentration [5.4 (4.4-7.9) ng/mL vs 12.2 (8.0-14.2) ng/mL, P < 0.01] resulted to be lower and High-sensitivity C reactive protein levels higher (4.21 ± 6.47 mg/L vs 0.98 ± 1.13 mg/L, P < 0.01) in the patient group. With respect to the lipoprotein profile, CD patients showed lower high density lipoproteincholesterol (HDL-C) (45 ± 15 mg/dL vs 57 ± 17 mg/dL, P < 0.05) and apo A-I (130 ± 31 mg/dL vs 155 ± 29 mg/ dL, P < 0.05) levels, as well as higher total cholesterol/ HDL-C [4.19 (3.11-5.00) vs 3.52 (2.84-4.08), P < 0.05] and apo B/apo A-I (0.75 ± 0.25 vs 0.55 ± 0.16, P < 0.05) ratios in comparison with control subjects. No statistically significant differences were detectedin lipoprotein-associated lipid transfer protein and enzymes.CONCLUSION: The presence and interaction of the detected alterations in patients with CD, would constitute a risk factor for the development of atherosclerotic cardiovascular disease.Fil: Tetzlaff, Walter Francisco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Meroño, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Menafra, Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Martin, Maximiliano. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Botta, Eliana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Matoso, María Dolores. Hospital Italiano; ArgentinaFil: Sorroche, Patricia Beatriz. Hospital Italiano; ArgentinaFil: De Paula, Juan A. Hospital Italiano; ArgentinaFil: Boero, Laura Estela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Brites, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentin

Aumento del riesgo de enfermedad cardiovascular en pacientes con enfermedad celíaca

En pacientes con enfermedad celíaca (EC), se ha observado mayor incidencia de eventos cardiovasculares que en controles, sin la presencia de factores de riesgo aterogénico clásicos. El objetivo de este estudio fue evaluar los factores de riesgo nóveles y biomarcadores de inflamación y enfermedad cardiovascular en pacientes con EC, con presentación típica y atípica. Fueron seleccionados 14 pacientes con EC sin tratamiento y controles pareados por sexo y edad. Se determinaron parámetros hematológicos, indicadores del metabolismo de los hidratos de carbono, proteína C reactiva ultrasensible (PCRus), per- fil lipoproteico y actividades de proteína transportadora de colesterol esterificado (CETP) y fosfolipasa A2 asociada a lipoproteínas (Lp-PLA2). Los pacientes con EC presentaron niveles plasmáticos mayores de insulina (7,2 mU/l vs. 4,4 mU/l; p<0,05) y mayor índice HOMA-IR (1,45 vs. 0,98; p<0,05) que los controles. Por otro lado, se observó menor concentración de colesterol-HDL (50 vs. 62 mg/dl; p<0,05), mayor cociente triglicéridos/colesterol-HDL y niveles de PCRus más altos (4,56 vs. 1,17 mg/l; p<0,05) en los pacientes que en los controles. Al comparar a los pacientes con presentación típica (n=8) y atí- pica (n=6), aquellos con presentación típica mostraron menores niveles de apo A-I (128 vs. 178 mg/dl; p<0,01) y aumento del cociente apo B/apo A-I (0,72 vs. 0,43; p<0,05), así como mayor actividad de LpPLA2 (7,9 umol/ml.h vs. 6,15 umol/ml.h; p<0,05). La interacción de las alteraciones descriptas durante períodos de tiempo prolongados en una condición patológica crónica como la EC constituirían un mayor riesgo de desarrollo de enfermedad cardiovascular aterosclerótica.In patients with celiac disease (CD), it has been reported higher incidence of cardiovascular events than in controls, without the presence of classical atherogenic risk factors. The aim of this study was to evaluate the novel risk factors and biomarkers of inflammation and cardiovascular disease in patients with CD, with typical and atypical presentation. We selected 14 patients with CD without treatment and 14 healthy sex and age-matched controls. Haematological parameters, indicators of carbohydrates metabolism, high sensitive C reactive protein (hsCRP), lipoprotein profile and the activities of cholesteryl ester transfer protein (CETP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were determined. CD patients presented higher insulin plasma levels (7.2 mU/l vs. 4.4 mU/l, p <0.05) and increased HOMA-IR index (1.45 vs. 0.98, p <0.05) than controls. On the other hand, lower HDLcholesterol concentration (50 vs. 62 mg/dl, p<0.05), higher TG/HDL-cholesterol ratio and increased hsCRP levels (4.56 vs. 1.17 mg / l, P <0.05) were observed in comparison with control subjects. When comparing patients with typical (n=8) and atypical (n=6) presentation, the former showed lower apo A-I levels (128 vs. 178 mg/dl, p<0.01), and higher apo B/apo A-I ratio (0.72 vs. 0.43, p<0.05) and LpPLA2 activity (7.9 umol/ml.h vs. 6.15 umol/ml.h, p<0.05). The interaction among the alterations above described during long periods of time in a chronic pathological condition such as CD could constitute higher risk of development of atherosclerotic cardiovascular disease.Fil: Menafra, Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Meroño, Tomás. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Matoso, María Dolores. Hospital Italiano; ArgentinaFil: Boero, Laura Estela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez Rosso, Leonardo Adrián. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Saez, María Soledad. Hospital Italiano; ArgentinaFil: Sorroche, Patricia Beatriz. Hospital Italiano; ArgentinaFil: de Paula, P.. Hospital Italiano; ArgentinaFil: Brites, Fernando Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Metabolic alterations, HFE gene mutations and atherogenic lipoprotein modifications in patients with primary iron overload

Abstract Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex-and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93 %, P &lt; 0.001). Metabolic profiles differed across HFE genotypes. C282Y homozygotes (n = 7) presented a reduced β-cell function and insulin secretion compared with non-C282Y patients (n = 11) (−58 % and −73 %, respectively, P &lt; 0.05). In addition, C282Y homozygotes featured a predominance of large, buoyant LDL particles (C282Y: 43 + − 5; non-C282Y: 25 + − 8; controls: 32 + − 7 %; P &lt; 0.001), whereas non-C282Y patients presented higher amounts of small, dense LDL (C282Y: 23 + − 5; non-C282Y: 39 + − 10; controls: 26 + − 4 %; P &lt; 0.01). HDL particles were altered in C282Y homozygotes. However, HDL functionality was conserved. In conclusion, metabolic alterations and HFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined

Juvenile exposure to a high fat diet promotes behavioral and limbic alterations in the absence of obesity

The incidence of metabolic disorders including obesity, type 2 diabetes and metabolic syndrome have seriously increased in the last decades. These diseases - with growing impact in modern societies - constitute major risk factors for neurodegenerative disorders such as Alzheimer's disease (AD), sharing insulin resistance, inflammation and associated cognitive impairment. However, cerebral cellular and molecular pathways involved are not yet clearly understood. Thus, our aim was to study the impact of a non-severe high fat diet (HFD) that resembles western-like alimentary habits, particularly involving juvenile stages where the brain physiology and connectivity are in plain maturation. To this end, one-month-old C57BL/6J male mice were given either a control diet or HFD during 4 months. Exposure to HFD produced metabolic alterations along with changes in behavioral and central parameters, in the absence of obesity. Two-month-old HFD mice showed increased glycemia and plasmatic IL1β but these values normalized at the end of the HFD protocol at 5 months of age, probably representing an acute response that is compensated at later stages. After four months of HFD exposure, mice presented dyslipidemia, increased Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, hepatic insulin resistance and inflammation. Alterations in the behavioral profile of the HFD group were shown by the impediment in nest building behavior, deficiencies in short and mid-term spatial memories, anxious and depressive- like behavior. Regarding the latter disruptions in emotional processing, we found an increased neural activity in the amygdala, shown by a greater number of c-Fos+ nuclei. We found that hippocampal adult neurogenesis was decreased in HFD mice, showing diminished cell proliferation measured as Ki67+ cells and neuronal differentiation in SGZ by doublecortin labeling. These phenomena were accompanied by a neuroinflammatory and insulin-resistant state in the hippocampus, depicted by a reactive phenotype in Iba1+ microglia cells (increased in number and soma size) and an impaired response to insulin given by decreased phosphorylated Akt levels and increased levels of inhibitory phosphorylation of IRS1. Our data portray a set of alterations in behavioral and neural parameters as a consequence of an early-life exposure to a quite moderate high fat diet, many of which can resemble AD-related features. These results highly emphasize the need to study how metabolic and neurodegenerative disorders are interrelated in deep, thus allowing the finding of successful preventive and therapeutic approaches.Fil: Vinuesa, María Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Pomilio, Carlos Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Menafra, Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Bonaventura, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Garay, Laura Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mercogliano, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Brites, Fernando Daniel. Universidad Nacional de Rosario. Facultad de Cs.bioquímicas y Farmaceuticas. Departamento de Bioquímica Clinica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Beauquis, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Saravia, Flavia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin

Associations between disease activity, markers of HDL functionality and arterial stiffness in patients with rheumatoid arthritis

Background and aims Rheumatoid arthritis (RA) is a chronic, inflammatory disease associated with increased risk of cardiovascular disease (CVD). Measures of HDL metabolism/function were shown to be altered in RA patients with high disease activity. We aimed at evaluating the effect of HDL characteristics on arterial stiffness in RA patients classified according to the inflammatory disease activity. Methods RA patients were classified according to disease activity (DAS-28) into active RA (n = 27; DAS-28 > 3.2) and inactive RA patients (n = 17; DAS-28 < 3.2). A control group of healthy individuals was also studied (n = 33). Clinical and biochemical characteristics, cholesteryl ester transfer protein (CETP) and paraoxonase 1 (phenylacetate and paraoxonase) activities and carotid-femoral pulse wave velocity (cf-PWV) were determined. Results Anthropometric characteristics were similar in all groups. In accordance with the inflammatory status, active RA patients presented elevated hsCRP levels (p < 0.001). There were no differences in the lipid profile between groups. Similarly, features of insulin resistance were absent in RA patients (p = non-significant). Active RA patients presented higher CETP activity than the other two groups (p = 0.026). Phenylacetate and paraoxonase activities were altered in active RA patients in comparison with the other groups (p = 0.034 and p = 0.041, respectively). Cf-PWV was significantly higher in active RA patients in comparison with controls, following adjustment by age (p = 0.030). Age (βst = 0.468, p = 0.013) and apo A-I levels (βst = −0.405, p = 0.029) were independent predictors of cf-PWV in a model including hsCRP, HOMA-IR, and phenylacetate activity (r2 = 0.42). Conclusions High DAS-28 identifies patients with alterations in HDL characteristics. Plasma levels of apo A-I can be used as a marker of arterial stiffness in RA.Fil: Botta, Eliana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Meroño, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Hospital Nacional "Profesor Alejandro Posadas"; ArgentinaFil: Saucedo, Carla. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Martin, Maximiliano Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Tetzlaff, Walter Francisco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Sorroche, Patricia Beatriz. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Boero, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Malah, Verónica. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Menafra, Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Gomez Rosso, Leonardo Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Chapman, John M.. Inserm; FranciaFil: Kontush, Anatol. Inserm; FranciaFil: Soriano, Enrique. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Brites, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin