Oxidative Stress in Obesity

Obesity is defined by the World Health Organization (WHO) as abnormal or excessive fat accumulation that presents a health risk [...

Fibrosis, the Bad Actor in Cardiorenal Syndromes: Mechanisms Involved

Cardiorenal syndrome is a term that defines the complex bidirectional nature of the interaction between cardiac and renal disease. It is well established that patients with kidney disease have higher incidence of cardiovascular comorbidities and that renal dysfunction is a significant threat to the prognosis of patients with cardiac disease. Fibrosis is a common characteristic of organ injury progression that has been proposed not only as a marker but also as an important driver of the pathophysiology of cardiorenal syndromes. Due to the relevance of fibrosis, its study might give insight into the mechanisms and targets that could potentially be modulated to prevent fibrosis development. The aim of this review was to summarize some of the pathophysiological pathways involved in the fibrotic damage seen in cardiorenal syndromes, such as inflammation, oxidative stress and endoplasmic reticulum stress, which are known to be triggers and mediators of fibrosis

Angiotensin II Promotes Skeletal Muscle Angiogenesis Induced by Volume-Dependent Aerobic Exercise Training: Effects on miRNAs-27a/b and Oxidant–Antioxidant Balance

Aerobic exercise training (ET) produces beneficial adaptations in skeletal muscles, including angiogenesis. The renin–angiotensin system (RAS) is highly involved in angiogenesis stimuli. However, the molecular mechanisms underlying capillary growth in skeletal muscle induced by aerobic ET are not completely understood. This study aimed to investigate the effects of volume-dependent aerobic ET on skeletal muscle angiogenesis involving the expression of miRNAs-27a and 27b on RAS and oxidant–antioxidant balance. Eight-week-old female Wistar rats were divided into three groups: sedentary control (SC), trained protocol 1 (P1), and trained protocol 2 (P2). P1 consisted of 60 min/day of swimming, 5×/week, for 10 weeks. P2 consisted of the same protocol as P1 until the 8th week, but in the 9th week, rats trained 2×/day, and in the 10th week, trained 3×/day. Angiogenesis and molecular analyses were performed in soleus muscle samples. Furthermore, to establish ET-induced angiogenesis through RAS, animals were treated with an AT1 receptor blocker (losartan). Aerobic ET promoted higher VO2 peak and exercise tolerance values. In contrast, miRNA-27a and -27b levels were reduced in both trained groups, compared with the SC group. This was in parallel with an increase in the ACE1/Ang II/VEGF axis, which led to a higher capillary-to-fiber ratio. Moreover, aerobic ET induced an antioxidant profile increasing skeletal muscle SOD2 and catalase gene expression, which was accompanied by high nitrite levels and reduced nitrotyrosine concentrations in the circulation. Additionally, losartan treatment partially re-established the miRNAs expression and the capillary-to-fiber ratio in the trained groups. In summary, aerobic ET promoted angiogenesis through the miRNA-27a/b–ACE1/Ang II/VEGF axis and improved the redox balance. Losartan treatment demonstrates the participation of RAS in ET-induced vascular growth. miRNAs and RAS components are promising potential targets to modulate angiogenesis for combating vascular diseases, as well as potential biomarkers to monitor training interventions and physical performance

Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress

We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI

Uso de Twitter y la gamificación para fomentar el análisis crítico del conocimiento científico y las vías para su comunicación en estudiantes del Grado de Medicina

El objetivo del proyecto de innovación docente que se presenta fue mejorar la capacidad de análisis crítico del conocimiento científico en el alumnado del Grado de Medicina a través del uso de Twitter. Los estudiantes de la asignatura de Fisiología Humana compartieron a través de Twitter noticias científicas relacionadas con la asignatura. Tras una selección previa, el profesorado publicó un periódico online y los alumnos presentaron una de las noticias publicadas. Se realizó una encuesta online de evaluación del proyecto utilizando escalas de Likert (1-10). Los estudiantes respondieron que el proyecto había aumentado su capacidad de análisis crítico de la investigación biomédica (7,65; ds=1,71) y que la metodología había aumentado su interés por la asignatura (8,05; ds=1,69). La utilización de Twitter combinada con la exposición de noticias científicas resultó útil para mejorar la capacidad de análisis crítico de la evidencia científica biomédica, competencia básica del Grado de Medicina

Instagram y gamificación para incorporar los procesos fisiológicos al día a día de los estudiantes de Fisiología

El presente proyecto de innovación docente se basa en la utilización de la red social Instagram para incentivar el estudio diario y el aprendizaje cooperativo de una forma lúdica, autónoma y divertida. Se aplicó en la docencia de la Fisiología Humana en distintos grados en los que participa el Departamento de Fisiología. La metodología consiste en que los alumnos, trabajando en grupo, publiquen contenidos en Instagram, para repasar, sintetizar y compartir información de la asignatura. Los objetivos alcanzados fueron: motivación en el estudio continuado, implicación en el proceso de aprendizaje, trabajo en equipo y adquisición de competencias transversales como creatividad, liderazgo y compromiso. La participación en el proyecto fue muy alta (94%), así como la satisfacción de los alumnos, sobre todo en aspectos motivacionales (interés y curiosidad por la asignatura) y de integración, gracias al trabajo en equipo. En conclusión, la red Instagram es una herramienta útil como complemento de las clases, con objeto de incentivar el estudio diario, sintetizar la información y transmitirla mediante trabajo cooperativo

Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve Alterations in an Experimental Pressure Overload Model

Galectin-3 (Gal-3) is involved in cardiovascular fibrosis and aortic valve (AV) calcification. We hypothesized that Gal-3 pharmacological inhibition with modified citrus pectin (MCP) could reduce aortic and AV remodeling in normotensive rats with pressure overload (PO). Six weeks after aortic constriction, vascular Gal-3 expression was up-regulated in male Wistar rats. Gal-3 overexpression was accompanied by an increase in the aortic media layer thickness, enhanced total collagen, and augmented expression of fibrotic mediators. Further, vascular inflammatory markers as well as inflammatory cells content were greater in aorta from PO rats. MCP treatment (100 mg/kg/day) prevented the increase in Gal-3, media thickness, fibrosis, and inflammation in the aorta of PO rats. Gal-3 levels were higher in AVs from PO rats. This paralleled enhanced AV fibrosis, inflammation, as well as greater expression of calcification markers. MCP treatment prevented the increase in Gal-3 as well as fibrosis, inflammation, and calcification in AVs. Overall, Gal-3 is overexpressed in aorta and AVs from PO rats. Gal-3 pharmacological inhibition blocks aortic and AV remodeling in experimental PO. Gal-3 could be a new therapeutic approach to delay the progression and the development of aortic remodeling and AV calcification in PO

The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study

The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of lepti

A Proteomic Approach to Determine Changes in Proteins Involved in the Myocardial Metabolism in Left Ventricles of Spontaneously Hypertensive Rats

Different works have suggested that in the hypertrophied heart the energy metabolic pathway shifts to glycolysis. Our aim was to evaluate using proteomics the expression of proteins associated with different energetic metabolic pathways in hypertrophied left ventricles of spontaneously hypertensive rats (SHR). Methods: 24-weeks-old SHR with stable hypertension and established left ventricle hypertrophy were used. Normotensive Wistar Kyoto rats were used as control. Proteins from left ventricles were analyzed by 2-dimensional electrophoresis and identified by comparison with a virtual rat heart proteomic map and mass spectrometry. Results: Enoyl-CoA hydratase expression, an enzyme involved in fatty acid β-oxidation, was reduced whereas the expression of other β-oxidation enzymes, 3-ketoacyl-CoA thiolase and the mitochondrial precursor of acyl-CoA thioester hydrolase, was increased in the hypertrophied left ventricles. The expression of two enzymes involved in the first steps of glycolysis, fructose bisphosphate aldolase and triosephosphate isomerase, was reduced in the left ventricle of SHR. Pyruvate dehydrogenase expression, enzyme involved in glucose oxidation, was enhanced in the hypertrophied ventricles whereas proteins of the tricarboxylic acid cycle were not modified. Proteins involved in the mitochondrial oxidative phosphorylation were overexpressed whereas the α-subunit of the mitochondrial precursor of ATP synthase was downexpressed. Conclusions: Several proteins involved in the main energy metabolic pathways were up and downexpressed. Moreover, our results seem to suggest that probably neither fatty acid β-oxidation nor glycolysis are the only sources for energy in the hypertrophied left ventricle.Ministerio de Sanidad y ConsumoInstituto de Salud Carlos IIIDepto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEpu