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Cardiovascular disease (CVD) is the leading cause of death worldwide and is the clinical manifestation of the atherosclerosis. Elevated LDL-cholesterol levels are the first line of therapy but the increasing prevalence in type 2 diabetes mellitus (T2DM) has positioned the cardiometabolic risk as the most relevant parameter for treatment. Therefore, the control of this risk, characterized by dyslipidemia, hypertension, obesity, and insulin resistance, has become a major goal in many experimental and clinical studies in the context of CVD. In the present review, we summarized experimental studies and clinical trials of recent anti-diabetic and lipid-lowering therapies targeted to reduce CVD. Specifically, incretin-based therapies, sodium-glucose co-transporter 2 inhibitors, and proprotein convertase subtilisin kexin 9 inactivating therapies are described. Moreover, the novel molecular mechanisms explaining the CVD protection of the drugs reviewed here indicate major effects on vascular cells, inflammatory cells, and cardiomyocytes, beyond their expected anti-diabetic and lipid-lowering control. The revealed key mechanism is a prevention of acute cardiovascular events by restraining atherosclerosis at early stages, with decreased leukocyte adhesion, recruitment, and foam cell formation, and increased plaque stability and diminished necrotic core in advanced plaques. These emergent cardiometabolic therapies have a promising future to reduce CVD burden.

Type 2 diabetes mellitus (T2DM) increases morbimortality in humans via enhanced susceptibility to cardiovascular disease (CVD). Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are drugs designed for T2DM treatment to diminish hyperglycaemia by reducing up to 90% of renal tube glucose reabsorption. Clinical studies also suggest a beneficial action of SGLT2i in heart failure and CVD independent of its hypoglycaemiant effect. In the present study, we explored the effect of SGLT2i dapagliflozin (DAPA) in the metabolism and atherosclerosis in Apoe&minus, /&minus, Irs2+/&minus, mice, which display accelerated atherosclerosis induced by insulin resistance. DAPA treatment of Apoe&minus, mice, which were fed a high-fat, high-cholesterol diet, failed to modify body weight, plasma glucose or lipid. Carbohydrate metabolism characterisation showed no effect of DAPA in the glucose tolerance test (GTT) despite augmented insulin levels during the test. In fact, decreased C-peptide levels in DAPA-treated mice during the GTT suggested impaired insulin release. Consistent with this, DAPA treatment of Apoe&minus, isolated islets displayed lower glucose-stimulated insulin secretion compared with vehicle-treated islets. Moreover, insulin-signalling experiments showed decreased pAKT activation in DAPA-treated adipose tissue indicating impaired insulin signalling in this tissue. No changes were seen in lesion size, vulnerability or content of macrophages, vascular smooth muscle cells, T cells or collagen. DAPA did not affect circulating inflammatory cells or cytokine levels. Hence, this study indicates that DAPA does not protect against atherosclerosis in insulin-resistant mice in hypercholesterolemic conditions.

Abdominal aortic aneurysm (AAA), is a complex disorder characterized by vascular vessel wall remodeling. LIGHT (TNFSF14) is a proinflammatory cytokine associated with vascular disease. In the present study, the impact of genetic inactivation of Light was investigated in dissecting AAA induced by angiotensin II (AngII) in the Apolipoprotein E-deficient (Apoe−/−) mice. Studies in aortic human (ah) vascular smooth muscle cells (VSMC) to study potential translation to human pathology were also performed. AngII-treated Apoe−/−Light−/− mice displayed increased abdominal aorta maximum diameter and AAA severity compared with Apoe−/− mice. Notably, reduced smooth muscle α-actin+ area and Acta2 and Col1a1 gene expression were observed in AAA from Apoe−/−Light−/− mice, suggesting a loss of VSMC contractile phenotype compared with controls. Decreased Opn and augmented Sox9 expression, which are associated with detrimental and non-contractile osteochondrogenic VSMC phenotypes, were also seen in AngII-treated Apoe−/−Light−/− mouse AAA. Consistent with a role of LIGHT preserving VSMC contractile characteristics, LIGHT-treatment of ahVSMCs diminished the expression of SOX9 and of the pluripotency marker CKIT. These effects were partly mediated through lymphotoxin β receptor (LTβR) as the silencing of its gene ablated LIGHT effects on ahVSMCs. These studies suggest a protective role of LIGHT through mechanisms that prevent VSMC trans-differentiation in an LTβR-dependent manner.

[EN] Traditional laboratory experiments are critical to the learning process across all areas and levels of study in science subjects. However, along with hands-on experiments, virtual labs have received considerable attention over the past several years due to the popularisation of ICT tools in Education, which may help teachers consider multiple learning styles to pursue meaningful learning. In this regard, studies concerning pupils’ experiences with both approaches are needed. The main aim of this study is to analyse the impact of the use of both virtual and hands-on labs in basic science subjects (BSS) in Health Sciences university degrees. For this reason, we have analysed different variables: general assessment, level of satisfaction, increase in motivation and increase in academic performance concerning BSS, as well as gender differences in the perception of both methodologies. A total of 129 undergraduate students from one Spanish university (degree in Dentistry) participated in the study. The results point out to statistically significant differences in favour of traditional labs in all the considered parameters. In conclusion, the results point out the importance of carrying out hands-on experiments to boost students’ motivation and performance, [ES] Las prácticas de laboratorio tradicionales juegan un papel protagonista en la enseñanza de las ciencias en todas las áreas y niveles. Sin embargo, en los últimos años la popularidad de los laboratorios virtuales ha aumentado significativamente, debido a que la aplicación de las herramientas TIC en educación permite atender adecuadamente a la diversidad del alumnado y fomentar el aprendizaje activo. En este sentido, resulta necesario estudiar las experiencias del alumnado con ambos enfoques. El principal objetivo de este estudio es analizar el impacto de los laboratorios virtuales y tradicionales en asignaturas de Ciencias Básicas (CCBB) en un grado de Ciencias de la Salud en el contexto universitario. Para ello se ha estudiado la valoración del alumnado, su grado de satisfacción general, su motivación y su rendimiento en las asignaturas de CCBB, así como la existencia de posibles diferencias de género. Los participantes del estudio fueron 129 estudiantes del grado en Odontología de una universidad española. Los resultados indican que existen diferencias significativas a favor de las prácticas tradicionales en todas las variables estudiadas. Como conclusión, se resalta la importancia de fomentar las prácticas tradicionales en grados de Salud para potenciar la motivación y el rendimiento del alumnado.