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The uncoupling protein UCP2 is a mitochondrial carrier for which transport activity remains controversial. The physiological contexts in which UCP2 is expressed have led to the assumption that, like UCP1, it uncouples oxidative phosphorylation and thereby reduces the generation of reactive oxygen species. Other reports have involved UCP2 in the Warburg effect, and results showing that UCP2 catalyzes the export of matrix C4 metabolites to facilitate glutamine utilization suggest that the carrier could be involved in the metabolic adaptations required for cell proliferation. We have examined the role of UCP2 in the energy metabolism of the lung adenocarcinoma cell line A549 and show that UCP2 silencing decreased the basal rate of respiration, although this inhibition was not compensated by an increase in glycolysis. Silencing did not lead to either changes in proton leakage, as determined by the rate of respiration in the absence of ATP synthesis, or changes in the rate of formation of reactive oxygen species. The decrease in energy metabolism did not alter the cellular energy charge. The decreased cell proliferation observed in UCP2-silenced cells would explain the reduced cellular ATP demand. We conclude that UCP2 does not operate as an uncoupling protein, whereas our results are consistent with its activity as a C4-metabolite carrier involved in the metabolic adaptations of proliferating cells.

Occlusions in the blood vessels caused by blood clots, referred to as thrombosis, and the subsequent outcomes are leading causes of morbidity and mortality worldwide. In vitro and in vivo models of thrombosis have advanced our understanding of the complex pathways involved in its development and allowed the evaluation of different therapeutic approaches for its management. This review summarizes different commonly used approaches to induce thrombosis in vivo and in vitro, without detailing the protocols for each technique or the mechanism of thrombus development. For ease of flow, a schematic illustration of the models mentioned in the review is shown below. Considering the number of available approaches, we emphasize the importance of standardizing thrombosis models in research per study aim and application, as different pathophysiological mechanisms are involved in each model, and they exert varying responses to the same carried tests. For the time being, the selection of the appropriate model depends on several factors, including the available settings and research facilities, the aim of the research and its application, and the researchers’ experience and ability to perform surgical interventions if needed.

RAICEX (Red de Asociaciones de Investigadores y Científicos Españoles en el Exterior),the Network of Associations of Spanish Researchers and Scientist Abroad, consists of more than 4,000 Spanish researchers distributed in 18 countries in 5 different continents.RAICEX was established in July 2018 by 15 foundational members: the associations of Spanish Researchers in the USA, México, Ireland, Sweden, Denmark, France, Italy,Japan, Australia, China, UK, Germany, Switzerland, Belgium, and Norway. Since then,3 more associations have joined: Emirates, Netherlands and South Africa. RAICEX was born with the main goal: “promoting the exchange of experiences and knowledge between Spanish researchers and scientists abroad and all the stakeholders of the Spanish System of Science, Technology and Innovation (SECTI), serving as an advisory body, information channel and catalyst for international relations in scientific matters,contributing to the progress of science.” Their main objectives are: (1) to provide support to researchers and scientists in mobility and personal development, offering training,information and guidance, as well as providing contact with all the other associations that make up the global network; (2) to disseminate and give visibility to the value of Science and the work of researchers and scientists, promoting communication of the advances of knowledge in all areas of society; (3) to promote international relations and cooperation between researchers / scientists and public and private organizations, from a global perspective; (4) to share the acquired knowledge and experience in different research and science systems abroad to advise, provide feedback and contribute to the progress of the whole SECTI. In this Case Study a particular scenario of the Spanish scientific diaspora, including history, reasons for going abroad, and consequences for the Spanish R&D system, shall be introduced to readers. The impact that RAICEX and its foundational members have had

[EN] Acute myocardial infarction and ischemic stroke are the two most frequent life-threatening presentations of atherosclerosis. These two conditions are the leading causes of morbidity and mortality worldwide. In both cases, the main determinant of poor outcome is the extent of irreversible injury. The mainstay treatment of acute myocardial infarction and ischemic stroke is timely reperfusion of the occluded artery to restore blood flow. However, despite being essential for tissue salvage, evidence shows that reperfusion itself triggers a set of potentially deleterious events that paradoxically contribute to final infarct size. From the different mechanisms involved in reperfusion-related injury, microvascular obstruction and acute inflammatory response play a central role. The beta-1-selective blocker metoprolol has been demonstrated to reduce myocardial infarct size through its inhibitory effect on neutrophils. Based on the cardioprotective effect of metoprolol injection, among other effects (e.g. antiarrhythmic effect); current clinical practice guidelines recommend early intravenous administration of beta-blockers to patients with an ongoing acute myocardial infarction. While different beta-blockers exist (with clear pharmacological differences among them), given the lack of comparative studies, clinical practice guidelines do not recommend on over another. While the adjuvant pharmacological treatment to reperfusion is well developed for acute myocardial infarction, treatment of stroke is currently restricted to reperfusion without coadjuvant therapies. Within this thesis, the biological effects of the different clinically available intravenous beta-blockers on different acute conditions have been tested. This work presents evidence that metoprolol has a particular action on neutrophils during exacerbated inflammation (acute myocardial infarction, peritonitis and acute lung injury) that affords a cardioprotection not provided by other beta-blockers, such as at, [ES] El infarto agudo de miocardio y el ictus isquémico son dos de las presentaciones de mayor frecuencia y potencialmente fatales de aterosclerosis. Estas dos condiciones son consideradas dos de las mayores causas de morbimortalidad a nivel mundial. En ambos casos, el principal determinante de un mal pronóstico es la extensión de la lesión irreversible. El principal tratamiento del infarto agudo de miocardio y el accidente cerebrovascular isquémico es la reperfusión de la arteria ocluida con el fin de restablecer el flujo sanguíneo. A pesar de ser esencial para la recuperación del tejido, la evidencia muestra que la reperfusión en sí desencadena una serie de eventos potencialmente nocivos que, paradójicamente, contribuyen al tamaño final del infarto. De los diferentes mecanismos implicados en la lesión por reperfusión, la obstrucción microvascular y la respuesta inflamatoria aguda juegan un papel central. La administración intravenosa previa a la reperfusión del antagonista beta-1-adrenérgico metoprolol ha demostrado ser capaz de reducir el tamaño del infarto de miocardio a través de su efecto inhibidor sobre los neutrófilos. Basándose en parte en el efecto cardioprotector de la inyección intravenosa de metoprolol, entre otros efectos (por ejemplo, su efecto antiarrítmico), las guías de práctica clínica actuales recomiendan la administración intravenosa temprana de beta-bloqueantes (como clase farmacoterapéutica) en pacientes con un infarto agudo de miocardio. Si bien existen diferentes beta-bloqueantes (con claras diferencias farmacológicas entre ellos), dada la falta de estudios comparativos, las guías de práctica clínica no recomiendan uno sobre otro. El tratamiento farmacológico adyuvante a la reperfusión está bien desarrollado para el infarto agudo de miocardio; sin embargo, el tratamiento actual del ictus isquémico se restringe a la reperfusión sin terapias coadyuvantes. En la presente tesis doctoral se han probado los efectos biológicos de los diferentes bet

Microvascular dysfunction and resulting tissue hypoxia is a major contributor to the pathogenesis and evolution of cardiovascular diseases (CVD). Diverse gene and cell therapies have been proposed to preserve the microvasculature or boost angiogenesis in CVD with moderate benefit. In this study, we tested in vivo the impact of sequential delivery by bone marrow cells of the pro-angiogenic factors vascular endothelial growth factor (VEGFA) and sphingosine-1-phosphate (S1P) in a myocardial infarction model. For that we transduced mouse bone marrow cells with lentiviral vectors coding for VEGFA or sphingosine kinase (SPHK1), which catalyzes S1P production, and injected them intravenously 4 and 7 days after cardiac ischemia/reperfusion in mice. Sequential delivery by transduced BM cells of VEGFA and S1P led to increased endothelial cell numbers and shorter extravascular distances in the infarct zone which support better oxygen diffusion 28 days post-MI as shown by automated 3D image analysis of the microvasculature. Milder effects were observed in the remote zone together with increased proportion of capillaries. BM cells delivering VEGFA and S1P also decreased myofibroblast abundance and restricted adverse cardiac remodeling without major impact on cardiac contractility. Our results indicate that BM cells engineered to sequentially deliver VEGFA/S1P angiogenic factors may constitute a promising strategy to improve micro-vascularization and oxygen diffusion thus limiting the adverse consequences of cardiac ischemia.