SR-B1, a Key Receptor Involved in the Progression of Cardiovascular Disease: A Perspective from Mice and Human Genetic Studies

High plasma level of low-density lipoprotein (LDL) is the main driver of the initiation and progression of cardiovascular disease (CVD). Nevertheless, high-density lipoprotein (HDL) is con-sidered an anti-atherogenic lipoprotein due to its role in reverse cholesterol transport and its ability to receive cholesterol that effluxes from macrophages in the artery wall. The scavenger receptor B class type 1 (SR-B1) was identified as the high-affinity HDL receptor, which facilitates the selective uptake of cholesterol ester (CE) into the liver via HDL and is also implicated in the plasma clearance of LDL, very low-density lipoprotein (VLDL) and lipoprotein(a) (Lp(a)). Thus, SR-B1 is a multifunc-tional receptor that plays a main role in the metabolism of different lipoproteins. The aim of this review is to highlight the association between SR-B1 and CVD risk through mice and human genetic studies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A mechanism-based operational definition and classification of hypercholesterolemia

In contrast to strong evidence-based clinical recommendations for lipid-lowering treatment, there is no analogous definitive diagnostic definition of hypercholesterolemia and its various subtypes. For many clinicians, guideline indications for hypolipidemic treatment can become broadly conflated with hypercholesterolemia in a non-specific sense. In this statement, we propose a unified definition and mechanism-based classification of hypercholesterolemia, which in turn should help to stratify patients and guide efficient diagnosis without interfering with the current strategies of ASCVD risk reduction

SR-B1, a Key Receptor Involved in the Progression of Cardiovascular Disease: A Perspective from Mice and Human Genetic Studies

High plasma level of low-density lipoprotein (LDL) is the main driver of the initiation and progression of cardiovascular disease (CVD). Nevertheless, high-density lipoprotein (HDL) is considered an anti-atherogenic lipoprotein due to its role in reverse cholesterol transport and its ability to receive cholesterol that effluxes from macrophages in the artery wall. The scavenger receptor B class type 1 (SR-B1) was identified as the high-affinity HDL receptor, which facilitates the selective uptake of cholesterol ester (CE) into the liver via HDL and is also implicated in the plasma clearance of LDL, very low-density lipoprotein (VLDL) and lipoprotein(a) (Lp(a)). Thus, SR-B1 is a multifunctional receptor that plays a main role in the metabolism of different lipoproteins. The aim of this review is to highlight the association between SR-B1 and CVD risk through mice and human genetic studies.This work was supported by grants from Gobierno de Aragón, B14–7R, Spain, and the Spanish Ministry of Science and Innovation PI18/01777, PI19/00694 and CIBERCV. These projects are co-financed by Instituto de Salud Carlos III and the European Regional Development Fund (ERDF) of the European Union ‘‘A way to make Europe’’. IG-R was funded by Sara Borrell fellowship CD19/00245

J-PLUS : the Javalambre Photometric Local Universe Survey

The Javalambre Photometric Local Universe Survey (J-PLUS ) is an ongoing 12-band photometric optical survey, observing thousands of square degrees of the Northern Hemisphere from the dedicated JAST/T80 telescope at the Observatorio Astrofísico de Javalambre (OAJ). The T80Cam is a camera with a field of view of 2 deg2 mounted on a telescope with a diameter of 83 cm, and is equipped with a unique system of filters spanning the entire optical range (3500–10 000 Å). This filter system is a combination of broad-, medium-, and narrow-band filters, optimally designed to extract the rest-frame spectral features (the 3700–4000 Å Balmer break region, Hδ, Ca H+K, the G band, and the Mg b and Ca triplets) that are key to characterizing stellar types and delivering a low-resolution photospectrum for each pixel of the observed sky. With a typical depth of AB ∼21.25 mag per band, this filter set thus allows for an unbiased and accurate characterization of the stellar population in our Galaxy, it provides an unprecedented 2D photospectral information for all resolved galaxies in the local Universe, as well as accurate photo-z estimates (at the δ z/(1 + z)∼0.005–0.03 precision level) for moderately bright (up to r ∼ 20 mag) extragalactic sources. While some narrow-band filters are designed for the study of particular emission features ([OII]/λ3727, Hα/λ6563) up to z <  0.017, they also provide well-defined windows for the analysis of other emission lines at higher redshifts. As a result, J-PLUS has the potential to contribute to a wide range of fields in Astrophysics, both in the nearby Universe (Milky Way structure, globular clusters, 2D IFU-like studies, stellar populations of nearby and moderate-redshift galaxies, clusters of galaxies) and at high redshifts (emission-line galaxies at z ≈ 0.77, 2.2, and 4.4, quasi-stellar objects, etc.). With this paper, we release the first ∼1000 deg2 of J-PLUS data, containing about 4.3 million stars and 3.0 million galaxies at r <  21 mag. With a goal of 8500 deg2 for the total J-PLUS footprint, these numbers are expected to rise to about 35 million stars and 24 million galaxies by the end of the survey

Hipospadias. A propósito de un caso de hipospadias proximal.

El hipospadias es la segunda malformación congénita más frecuente en varones, con una prevalencia de 1 de cada 250 recién nacidos, siendo el 15% formas proximales. Consiste en la localización anómala proximal del meato uretral, que se sitúa a lo largo del lado ventral del pene, escroto o periné. Se encuentra frecuentemente asociado a una incurvación ventral del pene (chordee) y a un defecto prepucial ventral. Esta anomalía se debe a un cierre incompleto de los pliegues uretrales durante la embriogénesis entre las semanas once y dieciséis. Su etiopatogenia es multifactorial, interviniendo factores de predisposición genética, estimulaciones hormonales prenatales inadecuadas, factores materno-placentarios e influencias medioambientales. Para su diagnóstico es importante contar con un equipo multidisciplinar, y su tratamiento consiste en la reparación quirúrgica. Se recomienda intervenir entre los 6 y los 18 meses de edad, corrigiendo la curvatura peneana y dejando un calibre adecuado del meato uretral en el glande, que permita una correcta función sexual y urinaria. Palabras clave: hipospadias, proximal, chordee, diferencia en el desarrollo sexual, etiología, epidemiología, cirugía, Bracka, complicaciones, resultados.<br /

Genetic predictors of weight loss in overweight and obese subjects

The aim of our study was to investigate a large cohort of overweight subjects consuming a homogeneous diet to identify the genetic factors associated with weight loss that could be used as predictive markers in weight loss interventions. We retrospectively recruited subjects (N = 788) aged over 18 years with a Body Mass Index (BMI) between 25 and 40 kg/m(2) who were treated at our lipid unit for at least one year from 2008 to 2016, and we also recruited a control group (168 patients) with normal BMIs. All participants received counselling from a nutritionist that included healthy diet and physical activity recommendations. We genotyped 25 single nucleotide variants (SNVs) in 25 genes that were previously associated with obesity and calculated genetic scores that were derived from 25 SNVs. The risk allele in CADM2 showed a higher frequency in overweight and obese subjects than in controls (p = 0.007). The mean follow-up duration was 5.58 +/- 2.68 years. Subjects with lower genetic scores showed greater weight loss during the follow-up period. The genetic score was the variable that best explained the variations in weight from the baseline. The genetic score explained 2.4% of weight change variance at one year and 1.6% of weight change variance at the end of the follow-up period after adjusting for baseline weight, sex, age and years of follow-up

Effect of bergamot on lipid profile in humans: A systematic review

Dyslipidemia is a well-established modifiable cardiovascular risk. Although statins can reduce LDLc by 50-60%, less than 20% of patients with high risk of CVD achieve LDL targets. The aim of this systematic review is to evaluate the effect of the nutraceutical, bergamot (Citrus bergamia), on lipid parameters in humans. PubMed, Embase, Cochrane Library, and Google Scholar databases were searched for interventional and observational studies investigating the effect of bergamot on lipid profile in humans. This systematic review retrieved a total of 442 studies of which 12 articles fulfilled the eligibility criteria and were included in the qualitative synthesis. Based on data, 75% of studies showed a significant decrease in total cholesterol, triglycerides and LDLc. The decrease in total cholesterol varied from 12.3% to 31.3%, from 7.6% to 40.8% in LDLc and from 11.5% to 39.5% in triglycerides. Eight trials reported HDLc increase after intervention with bergamot. Overall, a dose-dependent and possible synergistic effect when administering with statins can be deducted from these trials. It is essential to point out that studies had heterogeneous designs and scientific quality of studies was quite limited. Promising findings reveal an alternative therapeutic option in dyslipidemia management with bergamot supplementation, especially in subjects with statins intolerance

Association of cholesterol and oxysterols in adipose tissue with obesity and metabolic syndrome traits

Adipose tissue stores a substantial amount of body cholesterol in humans. Obesity is associated with decreased concentrations of serum cholesterol. During weight gain, adipose tissue dysfunction might be one of the causes of metabolic syndrome. The aim of this study is to evaluate cholesterol storage and oxidized metabolites in adipose tissue and their relationship with metabolic clinical characteristics

ABCG5/G8 gene is associated with hypercholesterolemias without mutation in candidate genes and non-cholesterol sterols

Context Approximately 20% to 40% of clinically defined familial hypercholesterolemia (FH) cases do not show a causative mutation in candidate genes (mutation-negative FH), and some of them may have a polygenic origin. Objective The aim of this work was to study the prevalence of ABCG5/G8 genetic variants in mutation-negative FH, as defects in these genes relate to intestinal hyperabsorption of cholesterol and thus ABCG5/G8 variants could explain in part the mechanism of hypercholesterolemia. Design, setting, and patients We sequenced the ABCG5/G8 genes in 214 mutation-negative FH and 97 controls. Surrogate markers of cholesterol absorption (5?-cholestanol, ?-sitosterol, campesterol, stigmasterol, and sitostanol) were quantified by high-performance liquid chromatography?tandem mass spectrometry in both studied groups. Results We found 8 mutation-negative FH patients (3.73%) with a pathogenic mutation in ABCG5/G8 genes. We observed significantly higher concentration of surrogate markers of cholesterol absorption in mutation-negative FH than in controls. In addition, we found significantly higher concentrations of cholesterol absorption markers in mutation-negative FH with ABCG5/G8 defects than in mutation-negative, ABCG5/G8-negative FH. A gene score reflecting the number of common single nucleotide variants associated with hypercholesterolemia was significantly higher in cases than in controls (P = .032). Subjects with a gene score above the mean had significantly higher 5?-cholestanol and stigmasterol than those with a lower gene score. Conclusions Mutation-negative FH subjects accumulate an excess of rare and common gene variations in ABCG5/G8 genes. This variation is associated with increased intestinal absorption of cholesterol, as determined by surrogate makers, suggesting that these loci contribute to hypercholesterolemia by enhancing intestinal cholesterol absorption.This study was supported by grants from the Spanish Ministry of Economy and Competitiveness PI15/01983, PI13/02507, PI12/01321, CIBERCV, CIBEROBN, and Cuenca Villoro Foundation. These projects are co-financed by Instituto de Salud Carlos III and the European Regional Development Fund (ERDF) of the European Union “A way to make Europe.