Spanish National Center for Cardiovascular Research

Madrid, Spain

Spanish National Center for Cardiovascular Research

Madrid, Spain

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Ledesma M.,Instituto Aragones Of Ciencias Of La Salud | Hurtado-Roca Y.,Spanish National Center for Cardiovascular Research | Leon M.,Instituto Aragones Of Ciencias Of La Salud | Giraldo P.,Instituto Aragones Of Ciencias Of La Salud | And 9 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: Ferritin concentration is associated with metabolic syndrome, but the possibility of a nonlinear association has never been explored. Objective: This study aimed to examine the relationship between serum ferritin levels and the metabolic syndrome in Spanish adult males. Design: This was a cross-sectional analysis of baseline data from the Aragon Workers' Health Study. Setting: Healthy workers from a factory were studied during their annual checkup. Participants: Spanish male adults (n = 3386) between the ages of 19 and 65 years participated. We excluded participants with ferritin > 500 μ/L, ferritin < 12 μg/L, or C-reactive protein > 10 mg/L. Main Outcome Measure: Metabolic syndrome was defined according to the 2009 consensus definition from the Joint Interim Statement of several international societies. Results: Metabolic syndrome prevalence was 27.1%. We found a positive association between elevated iron stores, measured as serum ferritin concentration, and metabolic syndrome and its criteria. Participants within the highest serum ferritin quintile had a higher risk than those in the lowest quintile for central obesity (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.46-2.42), hypertriglyceridemia (OR, 2.15; 95% CI, 1.69-2.74), and metabolic syndrome (OR, 1.92; 95% CI, 1.48-2.49). The association was nonlinear and occurred at serum ferritin concentrations > 100 μg/L (∼ 33th percentile). Ferritin was also associated with insulin resistance, measured by homeostatic model assessment-insulin resistance (HOMA-IR) (P trend < .001). Conclusions: Our findings suggest that serum ferritin is significantly associated with metabolic syndrome and its criteria (especially central obesity and hypertriglyceridemia), suggesting that ferritin could be an early marker of metabolic damage in the development of metabolic syndrome. Copyright © 2015 by the Endocrine Society.


Sanchez-Torres D.,Spanish National Center for Cardiovascular Research | Gutierrez-Bejarano D.,Spanish National Center for Cardiovascular Research | Hurtado-Roca Y.,Spanish National Center for Cardiovascular Research | Guallar-Castillon P.,Autonomous University of Madrid | And 4 more authors.
International Journal of Cardiology | Year: 2015

Background: Periodontal pathogens are associated with predisposition to chronic diseases and death. Antibody levels against them reflect flora burden, although high levels might indicate a protective response. We studied all-cause and cause specific mortality in relation to antibody levels in a representative US sample. Methods: Adults ≥20 years (n=6993) from the second phase of the Third National Health and Nutrition Examination Survey (NHANES III) were followed for a median of 13.2 years. Serum antibodies against Porphyromonas gingivalis (antiPG) and Actinobacillus actinomycetemcomitans (antiAA) were quantified by ELISA at baseline (1991-1994). Mortality hazard ratios (HRs) were calculated across antibody quartiles using the quartile with highest mortality as reference. Results: Median (25th, 75th percentiles) antiPG was 72 (63, 93) ELISA Units (EU) and median antiAA was 70 (64, 89) EU. After adjustment for potential confounders, mortality was highest for participants with antibodies in the third antiPG quartile (72-92 EU), with lower mortality risk for values not only below but also above this range [HR for the 1st to 4th quartiles: 0.81 (95% CI: 0.65, 1.01), 0.67 (95% CI: 0.55, 0.82), 1.00 (Reference), 0.79 (95% CI: 0.64, 0.97)]. In spline regression models the association had an inverted U-shape and mortality exhibited a peak at 84 EU (67th percentile). Mortality was not associated with antiAA. Conclusions: Mortality was highest for those just above the median antiPG and a reduced risk was present among those with lowor high levels of the antibody. Future studies should confirm this downward trend in upper levels and investigate a potential protective role of immunity against P. gingivalis. © 2015 Published by Elsevier Ireland Ltd.


Redondo S.,Complutense University of Madrid | Navarro-Dorado J.,Complutense University of Madrid | Ramajo M.,Complutense University of Madrid | Medina T.,Complutense University of Madrid | And 7 more authors.
Journal of Cardiothoracic Surgery | Year: 2014

Background: Transforming growth factor beta (TGF-β1) is a pleiotropic cytokine, which is deregulated in atherosclerosis; however the role of age in this process is unknown. We aimed to assess whether TGF-β1 signaling is affected by age.Methods: Vascular smooth muscle cells (VSMC) were obtained from patients undergoing abdominal surgery. Levels of TGF-β1 were measured by ELISA in sera from 169 patients undergoing coronary artery bypass grafting (CABG). The p27 expression was determined by Western blot from internal mammary arteries (IMA) obtained from CABG patients (n = 13). In VSMC from these patients undergoing abdominal surgery, secretion of TGF-β1 was determined by ELISA of cell-conditioned media.Results: In VSMC from aged patients we observed a lower TGF-β1 secretion, measured as TGF-β1 concentration in cell conditioned medium (p < 0.001). This effect was correlated to an age-dependent decrease of p27 expression in IMA from aged CABG patients. In a similar manner, there was an age-dependent decrease of serum TGF-β1 levels in CABG patients (p = 0.0195).Conclusions: VSMC from aged patients showed a higher degree of cellular senescence and it was associated to a lower TGF-β1 secretion and signaling. © 2014 Redondo et al.; licensee BioMed Central Ltd.


PubMed | Complutense University of Madrid, CIBER ISCIII, University of Missouri-St. Louis, Spanish National Center for Cardiovascular Research and 3 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome.We used baseline data from 3200 non-diabetic male participants in the Aragon Workers Health Study. We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI).Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMA-IR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering.HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome.


PubMed | Institute Investigacion Sanitaria Aragon, Spanish National Center for Cardiovascular Research, and Welch Center for Prevention, National-Louis University and CIBER ISCIII
Type: Comparative Study | Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD | Year: 2015

Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range.We studied 3533 male participants of the Aragon Workers Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration.TSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.


PubMed | Autonomous University of Madrid, Spanish National Center for Cardiovascular Research, National-Louis University and University of Alabama at Birmingham
Type: | Journal: International journal of cardiology | Year: 2015

Periodontal pathogens are associated with predisposition to chronic diseases and death. Antibody levels against them reflect flora burden, although high levels might indicate a protective response. We studied all-cause and cause specific mortality in relation to antibody levels in a representative US sample.Adults 20 years (n=6993) from the second phase of the Third National Health and Nutrition Examination Survey (NHANES III) were followed for a median of 13.2 years. Serum antibodies against Porphyromonas gingivalis (antiPG) and Actinobacillus actinomycetemcomitans (antiAA) were quantified by ELISA at baseline (1991-1994). Mortality hazard ratios (HRs) were calculated across antibody quartiles using the quartile with highest mortality as reference.Median (25th, 75th percentiles) antiPG was 72 (63, 93) ELISA Units (EU) and median antiAA was 70 (64, 89) EU. After adjustment for potential confounders, mortality was highest for participants with antibodies in the third antiPG quartile (72-92 EU), with lower mortality risk for values not only below but also above this range [HR for the 1st to 4th quartiles: 0.81 (95% CI: 0.65, 1.01), 0.67 (95% CI: 0.55, 0.82), 1.00 (Reference), 0.79 (95% CI: 0.64, 0.97)]. In spline regression models the association had an inverted U-shape and mortality exhibited a peak at 84 EU (67th percentile). Mortality was not associated with antiAA.Mortality was highest for those just above the median antiPG and a reduced risk was present among those with low or high levels of the antibody. Future studies should confirm this downward trend in upper levels and investigate a potential protective role of immunity against P. gingivalis.


Grisanti L.A.,Temple University | Gumpert A.M.,Temple University | Traynham C.J.,Temple University | Gorsky J.E.,Temple University | And 10 more authors.
Circulation | Year: 2016

Background: Immune cell-mediated inflammation is an essential process for mounting a repair response after myocardial infarction (MI). The sympathetic nervous system is known to regulate immune system function through β-adrenergic receptors (βARs); however, their role in regulating immune cell responses to acute cardiac injury is unknown. Methods: Wild-type (WT) mice were irradiated followed by isoform-specific βAR knockout (βARKO) or WT bone-marrow transplantation (BMT) and after full reconstitution underwent MI surgery. Survival was monitored over time, and alterations in immune cell infiltration after MI were examined through immunohistochemistry. Alterations in splenic function were identified through the investigation of altered adhesion receptor expression. Results: β2ARKO BMT mice displayed 100% mortality resulting from cardiac rupture within 12 days after MI compared with ≈20% mortality in WT BMT mice. β2ARKO BMT mice displayed severely reduced post-MI cardiac infiltration of leukocytes with reciprocally enhanced splenic retention of the same immune cell populations. Splenic retention of the leukocytes was associated with an increase in vascular cell adhesion molecule-1 expression, which itself was regulated via β-arrestin-dependent β2AR signaling. Furthermore, vascular cell adhesion molecule-1 expression in both mouse and human macrophages was sensitive to β2AR activity, and spleens from human tissue donors treated with β-blocker showed enhanced vascular cell adhesion molecule-1 expression. The impairments in splenic retention and cardiac infiltration of leukocytes after MI were restored to WT levels via lentiviral-mediated re-expression of β2AR in β2ARKO bone marrow before transplantation, which also resulted in post-MI survival rates comparable to those in WT BMT mice. Conclusions: Immune cell-expressed β2AR plays an essential role in regulating the early inflammatory repair response to acute myocardial injury by facilitating cardiac leukocyte infiltration. © 2016 American Heart Association, Inc.


Gonzalez M.A.,Spanish National Center for Cardiovascular Research | Bernad A.,Spanish National Center for Cardiovascular Research
Advances in Experimental Medicine and Biology | Year: 2012

Stem cells are characterized by their unlimited ability to divide specifically; a stem cell is capable of making an immense number of copies of itself, maintaining the same characteristics. Moreover, these cells are able to generate several of the cell lineages which make up the body, including cells from the heart, liver, kidney, neurons, and muscles. Investigation of the mechanisms through which this differentiation occurs, the genes involved and the possibility of increasing the efficiency with which stem cells can be isolated and/or characterized are currently among the most important fields in biology and biomedicine. To date, stems cells have been identified from four different sources: Embryonic stem cells (ESC), germinal stem cells, and those derived from embryonic carcinomas (teratocarcinomas) and from somatic tissues (somatic stem cells). The latter are called adult stem cells (ASC) when they are found in postnatal tissues. We now know that there is a great diversity among ASC, with some tissues, such as the bone marrow, containing more than one type of ASC. Adult stem cells have several characteristics that make them to be the main players in current regenerative medicine and are being investigated as potential therapeutic agents for a wide variety of diseases. Specifically, HSC and MSC are being assessed in increasing numbers of clinical trials. © 2012 Landes Bioscience and Springer Science+Business Media.


Callejas S.,Spanish National Center for Cardiovascular Research | Alvarez R.,Spanish National Center for Cardiovascular Research | Benguria A.,Spanish National Center for Cardiovascular Research | Dopazo A.,Spanish National Center for Cardiovascular Research
BioTechniques | Year: 2014

Next-generation sequencing (NGS) is becoming one of the most widely used technologies in the field of genomics. Library preparation is one of the most critical, hands-on, and time-consuming steps in the NGS workflow. Each library must be prepared in an independent well, increasing the number of hours required for a sequencing run and the risk of human-introduced error. Automation of library preparation is the best option to avoid these problems. With this in mind, we have developed automatic genomics NGS (AG-NGS), a computing application that allows an open liquid handling platform to be transformed into a library preparation station without losing the potential of an open platform. Implementation of AG-NGS does not require programming experience, and the application has also been designed to minimize implementation costs. Automated library preparation with AG-NGS generated high-quality libraries from different samples, demonstrating its efficiency, and all quality control parameters fell within the range of optimal values.


PubMed | Spanish National Center for Cardiovascular Research
Type: | Journal: Advances in experimental medicine and biology | Year: 2012

Stem cells are characterized by their unlimited ability to divide specifically; a stem cell is capable of making an immense number of copies of itself, maintaining the same characteristics. Moreover, these cells are able to generate several of the cell lineages which make up the body, including cells from the heart, liver, kidney, neurons, and muscles. Investigation of the mechanisms through which this differentiation occurs, the genes involved and the possibility of increasing the efficiency with which stem cells can be isolated and/or characterized are currently among the most important fields in biology and biomedicine.To date, stems cells have been identified from four different sources: Embryonic stem cells (ESC), germinal stem cells, and those derived from embryonic carcinomas (teratocarcinomas) and from somatic tissues (somatic stem cells). The latter are called adult stem cells (ASC) when they are found in postnatal tissues. We now know that there is a great diversity among ASC, with some tissues, such as the bone marrow, containing more than one type of ASC. Adult stem cells have several characteristics that make them to be the main players in current regenerative medicine and are being investigated as potential therapeutic agents for a wide variety of diseases. Specifically, HSC and MSC are being assessed in increasing numbers of clinical trials.

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