Colina, I. (Inmaculada)

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    Evaluation of measured and calculated small dense low-density lipoprotein in capillary blood and association with the metabolic syndrome
    (Elsevier, 2024) Deza, S. (Sara); Beloqui, O. (Óscar); Colina, I. (Inmaculada); Varo, N. (Nerea); Maroto-García, J. (Julia); Gonzalez-Hernandez, A. (Alvaro); Mugueta, C. (Carmen); Martínez-Chávez, E. (Estéfani); Monreal, J.I. (José Ignacio)
    Background and aims: Small-dense-low-density-lipoprotein cholesterol (sdLDL-C) is proatherogenic and not commonly measured. The aims were to evaluate capillary blood and its stability for sdLDL-C measurement and measure sdLDL-C in patients with metabolic syndrome (MS). Methods: 182 patients were studied (49 with MS). sdLDL-C was measured by electrophoresis (LipoPrint®), direct measurement (Roche Diagnostics) and Sampson equation. Intima-media thickness (IMT) and presence of atheroma was evaluated. sdLDL-C was compared in paired venous and capillary blood according to CLSI-EP09c (n = 40). sdLDL-C stability was studied after 24 h at room temperature (RT). Results: sdLDL-C in capillary blood and venous blood showed agreement with the direct measurement (bias: 4.17 mg/dL, LOA 95 %:-5.66; 13.99) and estimation (bias:8.12 mg/dL, LOA 95 %:-8.59; 24.82). sdLDL-C is stable in capillary blood for 24 h at RT. The electrophoretic method yielded lower (p < 0.05) sdLDL-C than the equation or direct measurement. Patients with MS had (p < 0.05) higher sdLDL-C (%) than patients without MS. Patients with atheroma plaques had higher sdLDL-C (p < 0.05). Estimated sdLDL-C correlated with IMT (r = 0.259, p < 0.001). Conclusions: Capillary blood is an alternative to venous blood for sdLDL-C measurement and is stable for 24 h after collection. Estimated and directly measured sdLDL-C associate with the MS being accessible tools for cardiovascular risk assessment.
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    Clinical usefulness of abdominal bioimpedance (ViScan) in the determination of visceral fat and its application in the diagnosis and management of obesity and its comorbidities
    (Elsevier, 2018) Valenti, V. (Víctor); Colina, I. (Inmaculada); Ramirez, B. (Beatriz); Benito-Boíllos, A. (Alberto); Catalan, V. (Victoria); Frühbeck, G. (Gema); Moncada, R. (Rafael); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Salvador, J. (Javier); Rodriguez, A. (Amaia); Gil, M.J. (María José); Romero, S. (Sonia); González-Crespo. I. (Ignacio)
    Background & aims: Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements. The measurement of VAT usually implies the use of imaging techniques such as magnetic resonance imaging or computed tomography (CT). Our aim was to evaluate the accuracy of the determination of VAT by means of abdominal bioimpedance (BIA) with the ViScan device in comparison with CT and its clinical usefulness in the management of obesity. Methods: We studied a sample of 140 subjects (73 males/67 females) with BMI ranging from 17.7 to 50.4 kg/m2 to evaluate the accuracy of the ViScan in comparison to CT to determine VAT. To further analyze ViScan's clinical usefulness we studied a separate cohort (n = 2849) analyzing cardiometabolic risk factors. Furthermore, we studied the ability of the ViScan to detect changes in VAT after weight gain (n = 107) or weight loss (n = 335). The study was performed from October 2009 through June 2015. Results: ViScan determines VAT with a good accuracy in individuals with a CT-VAT up to 200 cm2, and then with lower precision with increasing body mass, exhibiting a moderate-high correlation with CT-VAT (r = 0.75, P < 0.001). Importantly, VAT determination with the ViScan exhibits better correlations with several cardiometabolic risk factors such as glucose, triglycerides, HDL-cholesterol and markers of fatty liver than anthropometric measurements such as BMI or waist circumference. ViScan is able to detect VAT variations after body weight changes. Conclusions: Since the possibility of measuring VAT by imaging techniques is not always available, abdominal BIA represents a good alternative to estimate VAT, allowing the identification of patients with increased VAT-related cardiometabolic risk and a better management of obese patients.
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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.
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    Uroguanylin prevents hepatic steatosis, mitochondrial dysfunction and fibrosis in obesity-associated NAFLD
    (Elsevier, 2023) Valenti, V. (Víctor); Colina, I. (Inmaculada); Catalan, V. (Victoria); Becerril, S. (Sara); Frühbeck, G. (Gema); Fernández-Sáez, E.M. (Eva M.); Losarcos, M. (Maite); Burrell, M.A. (María Ángela); Martín, M. (Mariana); Moncada, R. (Rafael); Mugueta, C. (Carmen); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Escalada, J. (Javier)
    Background: The biological mediators supporting the resolution of liver steatosis, inflammation and fibrosis after bariatric surgery in patients with obesity and NAFLD remain unclear. We sought to analyze whether uroguanylin and guanylin, two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of obesity-associated NAFLD after bariatric surgery. Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 214 participants undergoing bariatric surgery with biopsy-proven NAFLD diagnosis. Pathways involved in lipid metabolism, mitochondrial network and fibrogenesis were evaluated in liver biopsies (n = 137). The effect of guanylin and uroguanylin on these metabolic functions was assessed in HepG2 hepatocytes and LX-2 hepatic stellate cells (HSC) under lipotoxic and profibrogenic conditions. Results: Plasma and hepatic expression of GUCA2B were decreased in obesity-associated NAFLD. Both GUCA2A and GUCA2B levels were increased after sleeve gastrectomy and Roux-en-Y gastric bypass in parallel to the improved liver function. The liver of patients with type 2 diabetes showed impaired mitochondrial β-oxidation, biogenesis, dynamics as well as increased fibrosis. Uroguanylin diminished the lipotoxicity in palmitate-treated HepG2 hepatocytes, evidenced by decresased steatosis and lipogenic factors, as well as increased mitochondrial network expression, AMPK-induced β-oxidation and oxygen consumption rate. Additionally, uroguanylin, but not guanylin, reversed HSC myofibroblast transdifferentiation as well as fibrogenesis after TGF-β1 stimulation. Conclusions: Uroguanylin constitutes a protective factor against lipotoxicity, mitochondrial dysfunction and fibrosis. Increased GUCA2B levels might contribute to improve liver injury in patients with obesity-associated NAFLD after bariatric surgery.
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    Association of age, inflammatory markers and subclinical atherosclerosis in subjects free from cardiovascular disease
    (Elsevier, 2008) Paramo, J.A. (José Antonio); Benito-Boilos, A. (Alberto); Beloqui, O. (Óscar); Colina, I. (Inmaculada); Diez-Martinez, J. (Javier); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio)
    BACKGROUND AND OBJECTIVE: We assessed whether an independent association between inflammatory markers and age-related subclinical atherosclerosis could be found in subjects free from cardiovascular disease. PATIENTS AND METHOD: Metabolic parameters, inflammatory and endothelial markers, such as high-sensitivity C-reactive protein, interleukin-6, fibrinogen and von Willebrand factor, as well as the carotid intima-media thickness were assessed in 890 asymptomatic subjects (mean age: 55 years; range: 20-80 years; 80% men) with cardiovascular risk factors. RESULTS: Subjects in the upper quartile (age 61-80 years) showed a significant increase of traditional risk factors, particularly arterial pressure and glucose levels (p < 0.01) as compared with lower quartiles. We also found a significant increase in the levels on inflammatory and endothelial markers (p < 0.001) and intima-media thickness (p < 0.001) in older adults. In the multivarate analysis, after adjustment for cardiovascular risk factors, intima-media thickness was independently associated with inflammation and endothelial dysfunction in older adults (p < 0.01). CONCLUSIONS: Besides age, systemic inflammation and vascular damage are associated with subclinical atherosclerosis in asymptomatic subjects. The age-related inflammatory profile may predispose to cardiovascular complications.
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    Association of SDF1 and MMP12 with atherosclerosis and inflammation: clinical and experimental study
    (MDPI, 2021) Paramo, J.A. (José Antonio); Colina, I. (Inmaculada); Machado, F. J. D. (Florencio J.D.); Marcos-Jubilar, M. (María); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio); Rodil-Fraile, R. (Raquel); Fernandez-Montero, A. (Alejandro); Roncal, C. (Carmen); Pastrana-Delgado, J. (Juan)
    Background: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in relation to atherosclerosis. Methods: Measurement of SDF1, MMP12 and CRP in blood samples of 298 prospective patients with cardiovascular risk. To explore atherosclerosis progression, CXCR4/SDF1 axis and MMP12 expression were determined by RT-qPCR and by immunohistochemistry in the aorta of accelerated and delayed atherosclerosis mice models (Apoe-/- and Apoe-/-Mmp10-/-). Results: SDF1, MMP12 and CRP were elevated in patients with clinical atherosclerosis, but after controlling by confounding factors, only SDF1 and CRP remained increased. Having high levels of both biomarkers showed 2.8-fold increased risk of presenting clinical atherosclerosis (p = 0.022). Patients with elevated SDF1, MMP12 and CRP showed increased risk of death in follow-up (HR = 3.2, 95%CI: 1.5-7.0, p = 0.004). Gene and protein expression of CXCR4 and MMP12 were increased in aortas from Apoe-/- mice. Conclusions: The combination of high circulating SDF1, MMP12 and CRP identified patients with particular inflammatory cardiovascular risk and increased mortality. SDF1/CXCR4 axis and MMP12 involvement in atherosclerosis development suggests that they could be possible atherosclerotic targets.
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    Independent association of fibrinogen with carotid intima-media thickness in asymptomatic subjects
    (Karger, 2003) Paramo, J.A. (José Antonio); Benito-Boilos, A. (Alberto); Irimia, P. (Pablo); Beloqui, O. (Óscar); Colina, I. (Inmaculada); Diez-Martinez, J. (Javier); Orbe, J. (Josune); Barba, J. (Joaquín); Zubieta, J.L. (José L.); Martinez-Vila, E. (Eduardo); Monreal, J.I. (José Ignacio)
    BACKGROUND: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. Both genetic and environmental factors contribute to its variability in plasma. However, whether the relation between fibrinogen and carotid intima-media thickness (IMT) is independent of those factors has not been established. Therefore, the aim of this study was to investigate the relations of plasma fibrinogens and the -455 G/A Bbeta-fibrinogen polymorphism with the carotid IMT in a series of asymptomatic subjects. METHODS: Markers of inflammation, C-reactive protein (CRP) and leukocytes, and endothelial perturbation (von Willebrand factor, vWF) were measured in 135 subjects. All individuals underwent a complete clinical examination and lipid measurements (cholesterol and its fractions HDL and LDL and triglycerides). The carotid IMT was measured by B-mode ultrasound in the common carotid artery. RESULTS: Patients in the highest fibrinogen tertile had a significantly higher BMI (p < 0.01), LDL-cholesterol (p < 0.01), leukocyte count, CRP and vWF (p < 0.001). In the univariate model a strong positive relationship was found between plasma fibrinogen and carotid IMT (p < 0.01). Fibrinogen also correlated positively with age, BMI, arterial systolic pressure, cholesterol, cholesterol-LDL, smoking, CRP and vWF (p < 0.01). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p < 0.01) after adjustment for all the parameters analyzed. CONCLUSION: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen was related to carotid IMT independent of a wide range of important confounding variables
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    Does chronic kidney disease facilitate malignant myocardial fibrosis in heart failure with preserved ejection fraction of hypertensive origin?
    (MDPI AG, 2020) Landecho, M.F. (Manuel F.); Eiros-Bachiller, R. (Rocío); Beloqui, O. (Óscar); Colina, I. (Inmaculada); Gavira, J.J. (Juan José); Ravassa, S. (Susana); Romero-González, G. (Gregorio); Gonzalez, A. (Arantxa); López, B. (Begoña); Diez, J. (Javier)
    In hypertensive patients with heart failure (HF) a serum biomarker combination of high carboxy-terminal propeptide of procollagen type-I (PICP) and low carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 (CITP:MMP-1) ratio identifies a histomolecular phenotype of malignant myocardial fibrosis (mMF) associated with severe diastolic dysfunction (DD) and poor outcomes. As chronic kidney disease (CKD) facilitates MF and DD, we investigated the influence of CKD on the mMF biomarker combination in HF patients with preserved ejection fraction (HFpEF). Hypertensives (n = 365), 232 non-HF and 133 HFpEF, were studied, and 35% non-HF and 46% HFpEF patients had CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio ≥ 30 mg/g). Specific immunoassays were performed to determine biomarkers. Medians were used to establish the high PICP and low CITP:MMP-1 combination. A comparison with non-HF showed that the biomarker combination presence was increased in HFpEF patients, being associated with CKD in all patients. CKD influenced the association of the biomarker combination and HFpEF (p for interaction ≤ 0.019). The E:e’ ratio was associated with the biomarker combination in CKD patients. Among CKD patients with HFpEF, those with the biomarker combination exhibited higher (p = 0.016) E:e’ ratio than those without the pattern. These findings suggest that CKD facilitates the development of biomarker-assessed mMF and DD in hypertensive HFpEF patients.
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    Ghrelin Reduces TNF-α-Induced Human Hepatocyte Apoptosis, Autophagy, and Pyroptosis: Role in Obesity-Associated NAFLD
    (Oxford University Press, 2019) Valenti, V. (Víctor); Ezquerro-Ezquerro, S. (Silvia); Colina, I. (Inmaculada); Catalan, V. (Victoria); Guzmán-Ruiz, R. (Rocío); Becerril, S. (Sara); Frühbeck, G. (Gema); Malagon, M.M. (María M.); Mugueta, C. (Carmen); Mocha, F. (Fátima); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Salvador, J. (Javier); Rodriguez, A. (Amaia)
    Context: Human obesity is associated with increased circulating TNF-α, a proinflammatory cytokine that induces hepatocyte cell death. Objective: The potential beneficial effects of acylated and desacyl ghrelin in the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis in obesity via the inhibition of TNF-α-induced hepatocyte apoptosis, autophagic cell death, and pyroptosis were investigated. Design, settings, and participants: Plasma ghrelin isoforms and TNF-α were measured in 158 participants, and hepatocyte cell death was evaluated in liver biopsies from 76 patients with morbid obesity undergoing bariatric surgery with available liver echography and pathology analysis. The effect of acylated and desacyl ghrelin on basal and TNF-α-induced cell death was determined in vitro in human HepG2 hepatocytes. Results: Circulating TNF-α and the acylated/desacyl ghrelin ratio were increased, whereas desacyl ghrelin levels were decreased in patients with obesity and NAFLD. Six months after bariatric surgery, decreased acylated/desacyl ghrelin levels, and improved hepatic function were found. Patients with obesity and type 2 diabetes showed increased hepatic ghrelin O-acyltransferase transcripts as well as an increased hepatic apoptosis, pyroptosis, and compromised autophagy. In HepG2 hepatocytes, acylated and desacyl ghrelin treatment reduced TNF-α-induced apoptosis, evidenced by lower caspase-8 and caspase-3 cleavage, as well as TUNEL-positive cells and pyroptosis, revealed by decreased caspase-1 activation and lower high-mobility group box 1 expression. Moreover, acylated ghrelin suppressed TNF-α-activated hepatocyte autophagy, as evidenced by a decreased LC3B-II/I ratio and increased p62 accumulation via AMPK/mTOR. Conclusions: Ghrelin constitutes a protective factor against hepatocyte cell death. The increased acylated/desacyl ghrelin ratio in patients with obesity and NAFLD might constitute a compensatory mechanism to overcome TNF-α-induced hepatocyte apoptosis, autophagy, and pyroptosis.
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    Adiponectin-leptin Ratio is a Functional Biomarker of Adipose Tissue Inflammation
    (MDPI AG, 2019) Colina, I. (Inmaculada); Ramirez, B. (Beatriz); Catalan, V. (Victoria); Becerril, S. (Sara); Frühbeck, G. (Gema); Gomez-Ambrosi, J. (Javier); Salvador, J. (Javier); Rodriguez, A. (Amaia)
    Obesity favors the development of cardiometabolic alterations such as type 2 diabetes (T2D) and the metabolic syndrome (MS). Obesity and the MS are distinguished by an increase in circulating leptin concentrations, in parallel to a drop in the levels of adiponectin. Consequently, the Adpn/Lep ratio has been suggested as a maker of dysfunctional adipose tissue. We aimed to investigate in humans (n = 292) the reliability of the Adpn/Lep ratio as a biomarker of adipose tissue dysfunction. We considered that an Adpn/Lep ratio of ≥1.0 can be considered normal, a ratio of ≥0.5 <1.0 suggests moderate-medium increased risk, and a ratio of <0.5 indicates a severe increase in cardiometabolic risk. Using these cut-offs, 5%, 54% and 48% of the lean, normoglycemic and without-MS subjects, respectively, fall within the group with an Adpn/Lep ratio below 0.5; while 89%, 86% and 90% of the obese, with T2D and with MS patients fall within the same group (p < 0.001). A significant negative correlation (r = -0.21, p = 0.005) between the Adpn/Lep ratio and serum amyloid A (SAA) concentrations, a marker of adipose tissue dysfunction, was found. We concluded that the Adpn/Lep ratio is a good indicator of a dysfunctional adipose tissue that may be a useful estimator of obesity- and MS-associated cardiometabolic risk, allowing the identification of a higher number of subjects at risk.