APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels

Abstract Apolipoprotein A5 gene (APOA5) variability explains part of the individual's predisposition to hypertriacylglycerolaemia (HTG). Such predisposition has an inherited component (polymorphisms) and an acquired component regulated by the environment (epigenetic modifications). We hypothesize that the integrated analysis of both components will improve our capacity to estimate APOA5 contribution to HTG. We followed a recruit-by-genotype strategy to study a population composed of 44 individuals with high cardiovascular disease risk selected as being carriers of at least one APOA5 SNP (-1131T>C and/or, S19W and/or 724C>G) compared against 34 individuals wild-type (WT) for these SNPs. DNA methylation patterns of three APOA5 regions [promoter, exon 2 and CpG island (CGI) in exon 3] were evaluated using pyrosequencing technology. Carriers of APOA5 SNPs had an average of 57.5 % higher circulating triacylglycerol (TG) levels (P = 0.039). APOA5 promoter and exon 3 were hypermethylated whereas exon 2 was hypomethylated. Exon 3 methylation positively correlated with TG concentration (r = 0.359, P = 0.003) and with a lipoprotein profile associated with atherogenic dyslipidaemia. The highest TG concentrations were found in carriers of at least one SNP and with a methylation percentage in exon 3 82 % (P = 0.009). In conclusion, CGI methylation in exon 3 of APOA5 acts, in combination with -1131T>C, S19W and 724C>G polymorphisms, in the individual's predisposition to high circulating TG levels. This serves as an example that combined analysis of SNPs and methylation applied to a larger set of genes would improve our understanding of predisposition to HTG

Association between exposure to air pollution and blood lipids in the general population of Spain.

Background and Aims: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain.Methods: We included 4647 adults (>18 years), participants in the national, cross- sectional, population- based [email protected] study, conducted in 2008– 2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1H- NMR lipoprotein test (Liposcale®). Participants were assigned air pollution con-centrations for particulate matter <10 μm (PM10), <2.5 μm (PM2.5) and nitrogen dioxide (NO2), corresponding to the health examination year, obtained by mod-elling combined with measurements taken at air quality stations (CHIMERE chemistry- transport model).Results: In multivariate linear regression models, each IQR increase in PM10, PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL- c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL- p) concentrations (p< .001 for all associations). In multivariate logistic regression, there was a significant associa-tion between PM10, PM2.5 and NO2 concentrations and the odds of presenting low HDL- c (<40 mg/dL), low HDL- p (<p25) and higher LDL particle (LDL- p) concentrations (≥p75). In subgroup analyses there were stronger associations be-tween PM10 and NO2 and low HDL- p in men (p for interaction .008 and .034), and between NO2 and low HDL- p in individuals with obesity (p for interaction .015).Conclusions: Our study shows an association between the exposure to air pol-lutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosisFunding for open access charge: Universidad de Málaga / CBU

Ressenya de l’informe Mengem futur, una reflexió sobre la sostenibilitat del sistema alimentari a Catalunya

The food system is becoming acknowledged as a key issue to progress towards the sustainability of our societies. According to the FAO, global food demand will have grown by 60% by 2050, while natural resources are becoming scarcer and the impacts of global change on agriculture are beginning to be noticed. In this context, the Advisory Council for Sustainable Development (CADS, from the Catalan), the advisory body on sustainability to the Catalan Government, approved the Feeding on future report in March 2018. This report seeks to analyse the main challenges and to put forward strategic proposals for action, resulting in a guarantee for Catalan food security. This paper sets out the report&rsquo;s main proposals and the foremost insights from the debate at the Catalan Institution for Agrarian Studies (ICEA, from the Catalan) presentation.Keywords: food security, food system, food, sustainability, sustainable development, 2030 Agenda, sustainable development goals.El sistema alimentario est&aacute; defini&eacute;ndose como una pieza clave para avanzar hacia la sostenibilidad de nuestras sociedades. Seg&uacute;n la Organizaci&oacute;n de las Naciones Unidas para la Alimentaci&oacute;n y la Agricultura (FAO), la demanda de alimentos a escala mundial habr&aacute; crecido un 60 % en 2050, mientras que los recursos naturales son cada vez m&aacute;s escasos y los impactos del cambio global sobre la producci&oacute;n agroalimentaria se hacen notar. En este contexto, en marzo de 2018, el Consejo Asesor para el Desarrollo Sostenible (CADS), &oacute;rgano asesor del Gobierno de Catalu&ntilde;a en el &aacute;mbito de la sostenibilidad, aprob&oacute; el informe Mengem futur, una reflexi&oacute;n sobre los principales retos que debe afrontar el sistema alimentario catal&aacute;n, con recomendaciones concretas para superarlos. Este art&iacute;culo recoge las principales propuestas del informe y las aportaciones m&aacute;s destacadas del debate que hubo en la presentaci&oacute;n a la Instituci&oacute; Catalana d&rsquo;Estudis Agraris (ICEA).Palabras clave: seguridad alimentaria, sistema alimentario, alimentaci&oacute;n, sostenibilidad, desarrollo sostenible, Agenda 2030, objetivos de desarrollo sostenible.El sistema alimentari s&rsquo;est&agrave; dibuixant com una pe&ccedil;a clau per a avan&ccedil;ar cap a la sostenibilitat de les nostres societats. Segons l&rsquo;Organitzaci&oacute; de les Nacions Unides per a l&rsquo;Alimentaci&oacute; i l&rsquo;Agricultura (FAO), la demanda d&rsquo;aliments a escala mundial haur&agrave; crescut un 60 % el 2050, mentre que els recursos naturals s&oacute;n cada cop m&eacute;s escassos i els impactes del canvi global sobre la producci&oacute; agroaliment&agrave;ria es fan notar. En aquest context, el mar&ccedil; de 2018, el Consell Assessor per al Desenvolupament Sostenible (CADS), &ograve;rgan assessor del Govern de Catalunya en l&rsquo;&agrave;mbit de la sostenibilitat, va aprovar l&rsquo;informe Mengem futur, una reflexi&oacute; sobre els principals reptes que ha d&rsquo;afrontar el sistema alimentari catal&agrave;, amb recomanacions concretes per tal de superar-los. Aquest article recull les principals propostes de l&rsquo;informe i les aportacions m&eacute;s destacades del debat que va tenir lloc en la presentaci&oacute; a la Instituci&oacute; Catalana d&rsquo;Estudis Agraris (ICEA).Paraules clau: seguretat aliment&agrave;ria, sistema alimentari, alimentaci&oacute;, sostenibilitat, desenvolupament sostenible, Agenda 2030, objectius de desenvolupament sostenible

Simvastatin Increases Fibulin-2 Expression in Human Coronary Artery Smooth Muscle Cells via RhoA/Rho-Kinase Signaling Pathway Inhibition

<div><p>The composition and structure of the extracellular matrix (ECM) in the vascular wall and in the atherosclerotic plaque are important factors that determine plaque stability. Statins can stabilize atherosclerotic plaques by modulating ECM protein expression. Fibulins are important components of the ECM. We evaluated the in vitro effect of simvastatin on the expression of fibulin-1, -2, -4 and -5 in human coronary artery smooth muscle cells (SMCs) and the mechanisms involved. Cells were incubated with simvastatin (0.05–1 μM), mevalonate (100 and 200 μM), geranylgeranyl pyrophosphate (GGPP) (15 μM), farnesyl pyrophosphate (FPP) (15 μM), the Rho kinase (ROCK) inhibitor Y-27632 (15 and 20 μM), the Rac-1 inhibitor (another member of Rho family) NSC23766 (100 μM), arachidonic acid (a RhoA/ROCK activator, 25–100 μM) and other fatty acids that are not activators of RhoA/ROCK (25–100 μM). Gene expression was analyzed by quantitative real-time PCR, and fibulin protein levels were analyzed by western blotting and ELISA. Simvastatin induced a significant increase in mRNA and protein levels of fibulin-2 at 24 hours of incubation (p<0.05), but it did not affect fibulin-1, -4, and -5 expression. Mevalonate and GGPP were able to reverse simvastatin’s effect, while FPP did not. In addition, Y-27632, but not NSC23766, significantly increased fibulin-2 expression. Furthermore, activation of the RhoA/ROCK pathway with arachidonic acid decreased fibulin-2 mRNA. Simvastatin increased mRNA levels and protein expression of the ECM protein fibulin-2 through a RhoA and Rho-Kinase-mediated pathway. This increase could affect the composition and structure of the ECM.</p></div

A: Effect of mevalonate on simvastatin-induced fibulin-2 mRNA levels in human coronary artery SMCs.

<p>Cells were preincubated for 2 hours with mevalonate (100, 200 μM) and treated with simvastatin for 24 hours. B: Effect of mevalonate on simvastatin-induced fibulin-2 protein levels in human coronary artery SMCs. Cells were preincubated for 2 hours with mevalonate (200 μM) and treated with simvastatin for 24 hours. Blot bands were normalized to actin and quantified with Quantity One Analysis Software version 4.6.2. A representative Western blot is shown. The results are shown as the mean with the standard error of the mean (SEM) for twelve independent experiments in 2A (2 with cell lot number 4C0915, 4 with cell lot number 4C1284, and 6 with cell lot number 886619) and six independent experiments in 2B (2 with cell lot number 4C0915, 2 with cell lot number 4C1284, and 2 with cell lot number 886619). Comparisons were performed using ANOVA followed by Dunett post-test correction.</p

Effect of simvastatin and mevalonate in secreted fibulin 2 expression in culture medium from human coronary artery SMCs.

<p>Cells were preincubated for 2 hours with mevalonate (200 μM) and treated with simvastatin for 24 hours. Blot bands were normalized to actin and quantified with Quantity One Analysis Software version 4.6.2. A representative Western blot is shown. The results are shown as the mean with the standard error of the mean (SEM) for four independent experiments in 3A (1 with cell lot number 4C1284 and 3 with cell lot number 886619) and three independent experiments in 2B with cell lot number 886619. Comparisons were performed using ANOVA followed by Dunett post-test correction.</p

Presentació del llibre: "Enric Freixa i Pedrals (1911-2002)" de Francesc X. Puig Rovira i Carles Puig-Pla

Enric Freixa i Perdals (Barcelona, 26 abril 1911 - 14 març 2002) Enginyer industrial per l'Escola d'Enginyers Industrials de Barcelona (1934). Professor adjunt (1942) de Càlcul integral i Mecànica racional; catedràtic (1947) d'Extensió de Càlcul i de Motors Tèrmics (1952). Subdirector de l'Escola (1955-1958 i 1965-1968) i secretari general de la Universitat Politècnica de Catalunya (1971-1981). Des de 1945, professor de l'Escola de Bibliotecàries. Enginyer a La Maquinista Terrestre i Marítima (1935-1971), on fou cap de la línia de motors dièsel, director comercial i assessor tècnic; ho alternà amb la tasca docent. Membre de l'Associació i del Col·legi d'Enginyers Industrials; fundador i president de la Mutualitat. Membre (1967) i president (1983-1995) de l'Acadèmia de Ciències i Arts de Barcelona. Membre de l'Institut d'Estudis Catalans. Membre fundador de la Societat de Tècnics d'Automoció (STA) i d'altres societats tècniques. Membre fundador i primer president (1977) de la Fundació Joaquim Torrens i Ibern per al foment del català al llenguatge científic i tècnic. Medalla Narcís Monturiol de la Generalitat de Catalunya (1985) al mèrit científic i tecnològic