Restituto, P. (Patricia)
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- Exploring the Association Between Emphysema Phenotypes and Low Bone Mineral Density in Smokers with and without COPD(2020) Seijo, L. (Luis); Campo, A. (Arantza); Colina, I. (Inmaculada); Calleja, M. (María); Bertó, J. (Juan); Torres, J.P. (Juan P.) de; Alcaide, A.B. (Ana Belén); Rodriguez-Fraile, M. (Macarena); González, J. (Jessica); Rivera-Ortega, P. (Pilar); Restituto, P. (Patricia); Perez-Warnisher, M.T. (María Teresa); Zulueta, J. (Javier); Varo-Cenarruzabeitia, M.N. (Miren Nerea)Rationale: Emphysema and osteoporosis are tobacco-related diseases. Many studies have shown that emphysema is a strong and independent predictor of low bone mineral density (BMD) in smokers; however, none of them explored its association with different emphysema subtypes. Objective: To explore the association between the different emphysema subtypes and the presence of low bone mineral density in a population of active or former smokers with and without chronic obstructive pulmonary disease (COPD). Methods: One hundred and fifty-three active and former smokers from a pulmonary clinic completed clinical questionnaires, pulmonary function tests, a low-dose chest computed tomography (LDCT) and a dual-energy absorptiometry (DXA) scans. Subjects were classified as having normal BMD or low BMD (osteopenia or osteoporosis). Emphysema was classified visually for its subtype and severity. Logistic regression analysis explored the relationship between the different emphysema subtypes and the presence of low BMD adjusting for other important factors. Results: Seventy-five percent of the patients had low BMD (78 had osteopenia and 37 had osteoporosis). Emphysema was more frequent (66.1 vs 26.3%, p=<0.001) and severe in those with low BMD. Multivariable analysis adjusting for other significant cofactors (age, sex, FEV1, and severity of emphysema) showed that BMI (OR=0.91, 95% CI: 0.76–0.92) and centrilobular emphysema (OR=26.19, 95% CI: 1.71 to 399.44) were associated with low BMD. Conclusion: Low BMD is highly prevalent in current and former smokers. BMI and centrilobular emphysema are strong and independent predictors of its presence, which suggests that they should be considered when evaluating smokers at risk for low BMD.
- Correlation between serum content of the main COPs (cholesterol oxidation products) from autoxidation and cardiovascular risk factors(Sociedad Española de Nutrición Parenteral y Enteral, 2011) Astiasarán, I. (Iciar); Ansorena-Artieda, D. (Diana); Menendez-Carreño, M. (María); Mugueta, C. (Carmen); Restituto, P. (Patricia); Varo-Cenarruzabeitia, M.N. (Miren Nerea)BACKGROUND/AIMS: Risk factors for cardiovascular disease (CVD) have been proven to be associated with an increased oxidative stress. Several studies have considered cholesterol oxidation products (COPs) as specific in vivo markers of oxidative stress. The aim of this study was to investigate the association between the levels of COPs derived from autoxidation processes and established cardiovascular risk factors, comparing the levels of serum COPs in subjects with or without showing values out of the reference ranges. METHODS: It was a cross-sectional study in which 88 subjects were recruited and individual and total COPs from autoxidation origin was analyzed in serum by GC-MS. The simultaneous correlation of COPs with different CVD risk factors have been analyzed. RESULTS AND DISCUSSION: A great variability of total COPs concentrations were found. Subjects presented total COPs values from 0.091 to 2.052 μg/mL. Total COPs were significantly higher (p < 0.05) in patients with hypertriglycerolemia, hypertension, diabetes and overweight/ obesity status compared to those subjects who did not present those CVD risk factors. Moreover, 7α and 7β hydroxycholesterol and 7-ketocholesterol were significantly higher (p < 0.05) in patients with hypertension and diabetes. No significant differences in total COPs were found between patients with and without hypercholesterolemia. CONCLUSIONS: The obtained results showed that the analyzed COPs correlate well with at least 4 out of 6 risk factors of development of CVD.
- Gender differences in plasma biomarker levels in a cohort of COPD patients: a pilot study(Public Library of Science, 2011) Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Baz-Dávila, R. (Rebeca); Cordoba-Lanus, E. (Elizabeth); Torres, J.P. (Juan P.) de; Aguirre-Jaime, A. (Armando); Pinto-Plata, V. (Víctor); Restituto, P. (Patricia); Varo-Cenarruzabeitia, M.N. (Miren Nerea)Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD). HYPOTHESIS: There are differences in serum biomarker levels between women and men with COPD. OBJECTIVE: Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD. METHODS: We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction. We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life. We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD. RESULTS: The plasma biomarkers level explored were similar in men and women without COPD. In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men. Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels. There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes. CONCLUSIONS: In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables. Further studies should confirm our findings.
- Adiponectin diminishes platelet aggregation and sCD40L release. Potential role in the metabolic syndrome(Endocrinology and Metabolism, 2010) Colina, I. (Inmaculada); Varo-Cenarruzabeitia, J.J. (José Javier); Restituto, P. (Patricia); Varo-Cenarruzabeitia, M.N. (Miren Nerea)The proinflammatory and proatherogenic mediator, soluble CD40 ligand (CD40L), is increased in the metabolic syndrome (MS) and released from platelets. We hypothesized that adiponectin modulates platelet function, and we sought to evaluate the association of adiponectin and sCD40L levels with platelet aggregation in MS and the effects of adiponectin on platelet aggregation and activation. Platelet aggregation and circulating adiponectin, sCD40L and P-selectin were determined in 30 controls and 30 patients with MS. Also, in vitro studies were performed in platelet-rich plasma from nine healthy volunteers. Adiponectin receptors were demonstrated by Western blotting and flow cytometry. ADP and epinephrine platelet aggregation was measured after preincubation with adiponectin. sCD40L and P-selectin secretion was measured in the supernatants by ELISA. Patients with MS had higher sCD40L and P-selectin than controls (5.96 +/- 0.50 vs. 4.28 +/- 0.41 ng/ml, P < 0.05, and 151 +/- 8 vs. 122 +/- 9 ng/ml, P < 0.05). By contrast, adiponectin was lower in patients with MS than in controls (5.25 +/- 0.30 vs. 7.35 +/- 0.34 microg/ml, P < 0.001). Higher platelet aggregation was found in MS. Adiponectin inversely correlated with P-selectin (R = -0.35, P = 0.009), sCD40L (r = -0.24, P = 0.05) and epinephrine and collagen induced aggregation (r = -0.80, P = 0.005; r = -0.70, P = 0.011). Platelets express the receptors for adiponectin. Platelet aggregatory response to epinephrine and ADP significantly decreased following preincubation with adiponectin (96 +/- 4 vs. 23 +/- 3%, P < 0.001, and 102 +/- 9 vs. 85 +/- 9%, P = 0.004). Adiponectin prevented platelet sCD40L release (1.63 +/- 0.15 vs. 2.04 +/- 0.20 ng/ml, P < 0.001). Enhanced platelet aggregation and activation markers are found in MS associated with low adiponectin concentrations. Novel evidence is provided demonstrating that adiponectin has antithrombotic properties, since it inhibits platelet aggregation and platelet activation.
- Cardiotrophin-1 is expressed in adipose tissue and upregulated in the metabolic syndrome(American Physiological Society, 2009) Colina, I. (Inmaculada); Diez-Martinez, J. (Javier); Fortuño, M.A. (María Antonia); Natal, C. (Cristina); Restituto, P. (Patricia); Bazan, A. (Antonio); Varo-Cenarruzabeitia, M.N. (Miren Nerea)Adipose tissue is a target for cardiotrophin-1 (CT-1), a cytokine member of the IL-6 family of cytokines that is involved in cardiac growth and dysfunction. However, it is unknown whether adipocytes are a source of CT-1 and whether CT-1 is overexpressed in diseases characterized by increased fat depots [i.e., the metabolic syndrome (MS)]. Thus this work aimed 1) to test whether adipose tissue expresses CT-1 and whether CT-1 expression can be modulated and 2) to compare serum CT-1 levels in subjects with and without MS diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria. Gene and protein expression of CT-1 was determined by real-time RT-PCR, ELISA, and Western blotting. CT-1 expression progressively increased, along with differentiation time from preadipocyte to mature adipocyte in 3T3-L1 cells. CT-1 expression was enhanced by glucose in a dose-dependent manner in these cells. mRNA and protein CT-1 expression was also demonstrated in human adipose biopsies. Immunostaining showed positive staining in adipocytes. Finally, increased CT-1 serum levels were observed in patients with MS compared with control subjects (127 +/- 9 vs. 106 +/- 4 ng/ml, P < 0.05). Circulating levels of CT-1 were associated with glucose levels (r = 0.2, P < 0.05). Taken together, our data suggest that adipose tissue can be recognized as a source of CT-1, which could account for the high circulating levels of CT-1 in patients with MS.
- The proinflammatory mediator CD40 ligand is increased in the metabolic syndrome and modulated by adiponectin(Endocrine Society, 2008) Colina, I. (Inmaculada); Diez-Martinez, J. (Javier); Natal, C. (Cristina); Restituto, P. (Patricia); Iñigo, C. (Carmen); Varo-Cenarruzabeitia, M.N. (Miren Nerea)OBJECTIVES: We hypothesized that the CD40/CD40 ligand (CD40L) system is up-regulated in the metabolic syndrome (MS) and modulated by adiponectin (AN). The objectives were: 1) to compare plasma and monocyte CD40L in patients with MS and controls and its association with clinical and biochemical parameters, 2) to investigate platelets as a source of soluble CD40L (sCD40L), and 3) to analyze the effects of AN on CD40/CD40L. METHODS: Plasma sCD40L and AN were measured in 246 controls and 128 patients with MS by ELISA. Monocyte CD40/CD40L expression and platelet CD40L content and release were compared in patients with MS and controls. Monocytes and endothelial cells were cultured with AN and CD40/CD40L expression determined by real-time RT-PCR and Western blotting. RESULTS: Patients with MS had higher sCD40L and lower AN levels than controls (0.89 +/- 0.1 vs. 0.76 +/- 0.07 ng/ml and 10.10 +/- 0.65 vs. 12.99 +/- 0.80 microg /ml, P < 0.05). Monocyte CD40/CD40L expression was higher (P < 0.05) in patients than controls (CD40: 1.31 +/- 0.31 vs. 0.80 +/- 0.14 arbitrary units; CD40L: 1.24 +/- 0.85 vs. 0.43 +/- 0.14 pg/microg protein). No differences were observed on CD40L content between resting platelets from patients with MS and controls (7.7 +/- 3.5 vs. 7.2 +/- 2.2 pg/microg protein). Stimulated platelets from patients with the MS released more (P < 0.05) sCD40L than controls (582 +/- 141 vs. 334 +/- 60% change vs. nonstimulated platelets). AN reduced CD40L mRNA and protein expression in monocytes from MS patients and endothelial cells. CONCLUSIONS: The enhanced sCD40L and cellular CD40L expression in the MS suggests that CD40L is of pathophysiological relevance in MS. Also, a new antiinflammatory effect of AN is described through the modulation of the CD40/CD40L system.
- Trabecular bone score in active or former smokers with and without COPD(Public Library of Science, 2019) Seijo, L. (Luis); Campo, A. (Arantza); Colina, I. (Inmaculada); Calleja, M. (María); Rivera, P. (Pilar); Bertó, J. (Juan); Torres, J.P. (Juan P.) de; Alcaide, A.B. (Ana Belén); Rodriguez-Fraile, M. (Macarena); González, J. (Jessica); Restituto, P. (Patricia); Pérez, T. (Teresa); Zulueta, J. (Javier); Varo-Cenarruzabeitia, M.N. (Miren Nerea)Background Smoking is a recognized risk factor for osteoporosis. Trabecular bone score (TBS) is a novel texture parameter to evaluate bone microarchitecture. TBS and their main determinants are unknown in active and former smokers. Objective To assess TBS in a population of active or former smokers with and without Chronic Obstructive Pulmonary Disease (COPD) and to determine its predictive factors. Methods Active and former smokers from a pulmonary clinic were invited to participate. Clinical features were recorded and bone turnover markers (BTMs) measured. Lung function, low dose chest Computed Tomography scans (LDCT), dual energy absorptiometry (DXA) scans were performed and TBS measured. Logistic regression analysis explored the relationship between measured parameters and TBS. Results One hundred and forty five patients were included in the analysis, 97 (67.8%) with COPD. TBS was lower in COPD patients (median 1.323; IQR: 0.13 vs 1.48; IQR: 0.16, p = 0.003). Regression analysis showed that a higher body mass index (BMI), younger age, less number of exacerbations and a higher forced expiratory volume-one second (FEV1%) was associated with better TBS (β = 0.005, 95% CI:0.000–0.011, p = 0.032; β = -0.003, 95% CI:-0.007(-)-0.000, p = 0.008; β = -0.019, 95% CI:-0.034(-)-0.004, p = 0.015; β = 0.001, 95% CI:0.000–0.002, p = 0.012 respectively). The same factors with similar results were found in COPD patients. Conclusions A significant proportion of active and former smokers with and without COPD have an affected TBS. BMI, age, number of exacerbations and the degree of airway obstruction predicts TBS values in smokers with and without COPD. This important information should be considered when evaluating smokers at risk of osteoporosis.