Núria Plana
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Featured researches published by Núria Plana.
American Journal of Cardiology | 1999
Josefa Girona; Agnes E. La Ville; Rosa Solà; Núria Plana; L. Masana
Treatment with statins are known to lower plasma and low-density lipoprotein (LDL) cholesterol levels with resultant prevention and regression of atherosclerosis. It has been recently suggested that the action of the statins may also have a direct effect on other mechanisms involved in the atherosclerotic plaque formation. Thus, we investigated whether simvastatin could have an antioxidant effect on plasma lipoproteins. The rate of oxidation of LDL and high-density lipoproteins (HDL) was measured by conjugated diene formation with and without the addition of increasing concentrations of simvastatin (in vitro) and in patients with and without treatment with simvastatin (in vivo). A strong correlation was observed between increasing simvastatin concentration and the lag phase, a negative correlation was observed for maximal rate and maximum diene production in LDL samples (r2 = +0.97, p <0.0001; r2 = -0.92, p <0.0001; r2 = -0.98, p <0.0001, respectively). For HDL no clear correlation could be established with the lag phase, but a strong negative correlation was also observed between simvastatin concentration and maximal rate and maximum diene production (r2 = -0.69, p <0.01; r2 = -0.98, p <0.0001, respectively). After 6 hours of oxidation the production of aldehydes in LDL and HDL was lower (30% and 5%, respectively) in samples obtained during simvastatin therapy with respect to those obtained without treatment. The 2,4-decadienal showed a decrease of 37% and 64% (p <0.05) in both oxidized-LDL and oxidized-HDL particles, respectively, with simvastatin treatment. Our findings demonstrate that simvastatin acts as an antioxidant in lipoprotein particles and, together with its lipid-lowering properties, could play an important role in preventing atherosclerosis.
American Journal of Cardiology | 2008
Fernando Civeira; Emilio Ros; Estíbaliz Jarauta; Núria Plana; Daniel Zambón; J. Puzo; Juan P. Martinez de Esteban; Juan Ferrando; Sergio Zabala; Fátima Almagro; Jose A. Gimeno; Luis Masana; Miguel Pocovi
Early diagnosis is important in familial hypercholesterolemia (FH), a highly atherogenic condition, but internationally agreed clinical diagnostic criteria are lacking. Genetic testing for low-density lipoprotein (LDL) receptor (LDLR) and apolipoprotein B (APOB) gene defects is the preferable diagnostic method, but the best phenotype indication to proceed with genetic diagnosis has not been established. The aim of this study was to assess the predictive and accuracy values of standard diagnostic criteria for detecting disease-causing mutations in 825 subjects with clinical FH aged > or =14 years from 3 lipid clinics in Spain. All subjects underwent thorough genetic testing for the detection of LDLR and APOB defects using the Lipochip platform. FH-causing mutations were detected in 459 subjects (55.6%). By logistic regression analysis, familial or personal history of tendon xanthoma (TX) and LDL cholesterol were strongly associated with genetic diagnosis (p <0.005, R(2) = 0.41). In subjects without familial or personal histories of TX, the diagnostic criteria for FH of the Make Early Diagnosis to Prevent Early Deaths (MEDPED) project, based on age-specific LDL cholesterol thresholds, showed sensitivity of 72.4%, specificity of 71.1%, and accuracy of 71.6%. LDL cholesterol > or =190 mg/dl in subjects with familial or personal histories of TX and > or =220, > or =225, and > or =235 mg/dl in those without such histories aged <30, 30 to 39, and > or =40 years, respectively, showed sensitivity of 91.1%, specificity of 71.1%, and accuracy of 74.2% for a positive genetic diagnosis. This new set of diagnostic criteria for FH was validated in an independent group of 440 subjects from 6 additional Spanish lipid clinics. In conclusion, TX and age-adjusted LDL cholesterol cut-off values have the highest value for clinical diagnosis and indication of genetic testing in FH.
Atherosclerosis | 2010
Gemma Aragonès; Raimon Ferré; Iolanda Lázaro; Anna Cabré; Núria Plana; Jordi Merino; Mercedes Heras; Josefa Girona; L. Masana
OBJECTIVE Adipocyte fatty acid-binding protein (FABP4) plasma levels are higher in type 2 diabetes (T2D). Endothelial dysfunction is also common in T2D. We have investigated the relationship between circulating FABP4 levels and endothelial function in diabetic patients. METHODS In 257 patients (105 diabetic and 152 non-diabetic) at increased risk of cardiovascular disease, we measured circulating FABP4, reactive hyperemia index (RHI) by peripheral artery tonometry, intima-media thickness, and biomarkers of inflammation, oxidation and endothelial function. RESULTS In T2D subjects, FABP4 was negatively associated with endothelial function, as measured by RHI (r=-0.226, P=0.05). In a stepwise multivariate linear regression model, FABP4 was a predictor of RHI in T2D patients (P=0.04). CONCLUSION Circulating levels of FABP4 are inversely associated with endothelial function in T2D patients, as measured by RHI. We suggest a direct effect of plasma FABP4 on the vascular endothelium in those with T2D.
Atherosclerosis | 2011
María Solanas-Barca; Isabel De Castro-Orós; Rocío Mateo-Gallego; Montserrat Cofán; Núria Plana; J. Puzo; Elena Burillo; Paula Martín-Fuentes; Emilio Ros; Luis Masana; Miguel Pocovi; Fernando Civeira; Ana Cenarro
OBJECTIVE Rare mutations in the APOE gene, undetectable with the usual genotyping technique, are responsible for dominant familial dysbetalipoproteinemia (FD) and therefore could be easily misclassified as familial combined hyperlipidemia (FCHL). We aimed to identify APOE mutations associated with dominant combined hyperlipoproteinemia and to establish their frequency in subjects with a clinical diagnosis of FCHL. METHODS AND RESULTS In 279 unrelated subjects with FCHL in whom a functional LDLR mutation was excluded, sequencing of the entire APOE gene detected 9 carriers of a rare mutation: 5 subjects (1.8%) with the R136S mutation (arginine at residue 136 changed to serine) and 4 subjects (1.4%) with the p.Leu149del mutation, a 3-bp inframe deletion that results in the loss of leucine at position 149. Both genetic defects were detected with similar frequency (2.5% and 1.3%, respectively) in an independent group of 160 FCHL subjects from other locations in Spain. Family studies demonstrated cosegregation of these APOE mutations with hyperlipoproteinemia. R136S carriers showed dysbetalipoproteinemia, while the lipid phenotype of p.Leu149del carriers was IIa or IIb. CONCLUSIONS Rare APOE mutations are responsible for approximately 3.5% of FCHL cases in our population. APOE R136S and p.Leu149del induce autosomal dominant FD and a phenotype indistinguishable from FCHL, respectively.
Journal of Lipid Research | 2015
Roger Mallol; Núria Amigó; Miguel Á. Rodríguez; Mercedes Heras; Maria Vinaixa; Núria Plana; Edmond Rock; Josep Ribalta; Oscar Yanes; L. Masana; X. Correig
Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion-ordered 1H NMR spectroscopy. Our method uses diffusion coefficients to provide a direct measure of the mean particle sizes and numbers. Using 177 plasma samples from healthy individuals and the concentration of ApoB and ApoA from isolated lipoprotein fractions, our test showed a stronger correlation between the NMR-derived lipoprotein particle numbers and apolipoprotein concentrations than the LipoProfile® test commercialized by Liposcience. We also converted LDL particle numbers to ApoB equivalents (milligrams per deciliter) and our test yielded similar values of LDL-ApoB to the LipoProfile® test (absolute mean bias of 8.5 and 7.4 mg/dl, respectively). In addition, our HDL particle number values were more concordant with the calibrated values determined recently using ion mobility. Finally, principal component analysis distinguished type 2 diabetic patients with and without atherogenic dyslipidemia (AD) on a second cohort of 307 subjects characterized using the Liposcale test (area under the curve = 0.88) and showed concordant relationships between variables explaining AD. Altogether, our method provides reproducible and reliable characterization of lipoprotein particles and it is applicable to pathological states such as AD.
PLOS ONE | 2013
Josefa Girona; Roser Rosales; Núria Plana; Paula Saavedra; L. Masana; Joan-Carles Vallvé
Purpose The migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs). Methods and Results A DNA 5-bromo-2′-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml) significantly inhibited the induced cell proliferation, demonstrating the specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs. unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4 significantly increased cell migration compared with unstimulated cells from 4 h (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5 µM) and PD98059 (10 µM) blocked the FABP4-induced proliferation and migration of HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we observed an up-regulation of the MAPK pathway without activation of Akt. We found that FABP4 induced the active forms of the nuclear transcription factors c-jun and c-myc, which are regulated by MAPK cascades, and increased the expression of the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are involved in cell cycle regulation and cell migration. Conclusions These findings indicate a direct effect of FABP4 on the migration and proliferation of HCASMCs, suggesting a role for this adipokine in vascular remodelling. Taken together, these results demonstrate that the FABP4-induced DNA synthesis and cell migration are mediated primarily through a MAPK-dependent pathway that activates the transcription factors c-jun and c-myc in HCASMCs.
Circulation-cardiovascular Genetics | 2016
Rosa M. Sánchez-Hernández; Fernando Civeira; Marianne Stef; Sofía Pérez-Calahorra; Fátima Almagro; Núria Plana; Francisco J. Nóvoa; Pedro Sáenz-Aranzubía; Daniel Mosquera; Cristina Soler; Francisco Fuentes; Yeray Brito-Casillas; José T. Real; Francisco Blanco-Vaca; Juan F. Ascaso; Miguel Pocovi
Background— Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and LDL protein receptor adaptor 1 ( LDLRAP1 ). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results— Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH—of whom, 47 were true homozygous (1 for APOB , 5 for LDLRAP1 , and 41 for LDLR ), 45 compound heterozygous for LDLR , 3 double heterozygous for LDLR and PSCK9 , and 2 double heterozygous for LDLR and APOB . No PSCK9 homozygous cases were identified. Two variants in LDLR were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1:450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events. Conclusions— HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy.Background—Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results—Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH—of whom, 47 were true homozygous (1 for APOB, 5 for LDLRAP1, and 41 for LDLR), 45 compound heterozygous for LDLR, 3 double heterozygous for LDLR and PSCK9, and 2 double heterozygous for LDLR and APOB. No PSCK9 homozygous cases were identified. Two variants in LDLR were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1:450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events. Conclusions—HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy.
Journal of Lipid Research | 2010
Anna Cabré; Iolanda Lázaro; Montserrat Cofán; Estíbaliz Jarauta; Núria Plana; Ángel Luis García-Otín; Juan F. Ascaso; Raimon Ferré; Fernando Civeira; Emilio Ros; L. Masana
The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) microg/l and 19.2 (9.2) microg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia.
Atherosclerosis | 2011
Raimon Ferré; Gemma Aragonès; Núria Plana; Jordi Merino; Merche Heras; Carme Buixadera; Luis Masana
OBJECTIVE Reactive hyperaemia after shear stress is a surrogate marker of endothelial function. However, the mechanisms controlling the dilation capacity of small peripheral resistance arteries are not well characterised. We evaluated reactive hyperaemia by peripheral artery tonometry (PAT) in the acral arteries and studied their clinical and biochemical determinants. METHODS Eight hundred sixteen subjects at intermediate to high cardiovascular risk were recruited. The reactive hyperaemia index (RHI) of small digital arteries was measured by PAT. Clinical history data, anthropometry and biochemical parameters were also analysed. We studied the associations between clinical and biochemical factors and small artery RHI. RESULTS HDL cholesterol and apolipoprotein A1 levels were strongly and directly correlated with an increased dilation response. Metabolic syndrome components, such as increased waist circumference, hypertriglyceridaemia and smoking, were inversely associated with RHI as were serum markers of inflammation. The predictors of small peripheral artery RHI were HDL cholesterol, which had a protective effect, and smoking, which had a negative impact. CONCLUSION HDL cholesterol and apolipoprotein A1 levels had a strong, positive correlation with small artery reactive hyperaemia, whereas smoking, waist circumference and triglyceride levels were inversely associated. HDL cholesterol was the main determinant of RHI in small peripheral resistance arteries.
Human Mutation | 2011
Isabel De Castro-Orós; Sandra Pampín; Alfonso Bolado-Carrancio; Aguirre de Cubas; Lourdes Palacios; Núria Plana; José Puzo; Esperanza Martorell; Marianne Stef; Luis Masana; Fernando Civeira; José Carlos Rodríguez-Rey; Miguel Pocovi
Familial hypercholesterolemia (FH) is a dominant disorder due to mutations in the LDLR gene. Several mutations in the LDLR promoter are associated with FH. Screening of 3,705 Spanish FH patients identified 10 variants in the promoter and 5′ UTR. Here, we analyse the functionality of six newly identified LDLR variants. Mutations located in the LDLR promoter regulatory elements R2 and R3 (c.−155_‐150delACCCCinsTTCTGCAAACTCCTCCC, c.−136C>G, c.−140C>G, and c.−140C>T) resulted in 6 to 15% residual activity in reporter expression experiments and changes in nuclear protein binding affinity compared to wild type. No reduction was observed when cells were transfected with c.−208T, c.−88A, and c.−36G mutant fragments. Our results indicate that mutations localized in R2 and R3 are associated with hypercholesterolemia, whereas mutations outside the LDLR response elements are not a cause of FH. This data emphasizes the importance of functional analysis of variants in the LDLR promoter to determine their association with the FH phenotype.Hum Mutat 32:1–5, 2011.