Molecular mechanisms of cardiovascular calcification

Cardiovascular calcification is a pathophysiological process characterized by the deposition of calcium-phosphate crystals in the arteries and the leaflets of the heart valves. In the arteries calcification causes arterial stiffness, which may lead to poor cardiac perfusion, systolic hypertension and heart failure. In the aortic valve, calcification causes left ventricular outflow obstruction. Currently, no medical treatment exists to halt or reverse cardiovascular calcification. For that reason, understanding the molecular mechanisms underlying cardiovascular calcification is of particular importance. Molecularly, cardiovascular calcification is a continuum comprising intertwined physicochemical and biologically active processes. In particular, cardiovascular calcification commences when cells become overburdened by the mineral imbalance typical of chronic kidney disease (CKD), or the unresolved inflammation characteristic of atherosclerosis and aortic valve stenosis (AVS). These alterations in homeostasis lead to changes in the fate and phenotype of structural cells such as vascular smooth muscle cells (VSMCs) and valvular interstitial cells (VICs). This phenotypic switch is characterized by: the loss of calcification inhibitors, an increase in pro-osteogenic signaling, changes in proliferation, abnormal processing and synthesis of extracellular matrix (ECM), and alterations in autophagy. In the current thesis, three pathways relevant to cardiovascular calcification are discussed. First, in Articles I and II, the G-protein coupled receptor ChemR23 arises as a promoter of a synthetic and proliferative VSMC phenotype, prone to phosphate-induced calcification. Importantly, this phenotype could be reverted by genetic deletion of ChemR23, and calcification was inhibited by the ChemR23 ligands: RvE1 and chemerin. Translationally, chemerin was negatively associated with coronary artery calcification in CKD patients. Moreover, in Article III, ChemR23 expressed in macrophages, promoted the resolution of inflammation, and inhibited VSMC proliferation in a mouse model of intimal hyperplasia. Secondly, Article IV demonstrates that iron, preferentially present in the calcified regions of the aortic valve, accumulated in VICs. This uptake of iron enhanced VIC proliferation and actively contributed to the ECM remodeling. Finally, Article V reveals a detrimental role of the second generation tyrosine kinase inhibitor nilotinib on the aortic valve. In vivo, nilotinib promoted aortic valve thickening. In vitro, nilotinib enhanced VIC osteoblastic trans- differentiation, increased calcification and inhibited autophagy. Mechanistically, nilotinib preferentially inhibited the most abundant collagen sensing tyrosine kinase in the valve: the discoidin domain receptor 2. Overall the results from this thesis suggests that changes in VSMC and VIC phenotype, as well as alterations in the ECM content and sensing can have profound effects on cardiovascular calcification, and therefore serve as potential therapeutic targets

Housing in the first periphery of Barcelona: towards the finding of criteria for urban renewal

During the mid XX th century the former outskirts of Barcelona was the field of an unprecedented urbanization process addressed to housing purposes. A very heterogeneous system of settlements occupied the steep hillsides of Tres Turons and Collserola. These former deprived residential suburbs became, in less than twenty years, fully urban neighbourhoods with extreme densities and urgent needs. From beginning the 80’ to our days “Barcelona on slope” has become the conceptual and physical frame for urban renewal policies. Although there’s still much to do, the large amount of accomplished plans and actions calls for an evaluation and a synthesis from which probable criteria for future actions can be inferred.Postprint (published version

A Methodology to Analyze the Presence of Sustainability in Engineering Curricula. Case of Study: Ten Spanish Engineering Degree Curricula

This paper presents a methodology to analyze the sustainability presence level in the curriculum of an engineering degree. The methodology is applied to ten engineering degrees of the Spanish university system, taught in three di erent universities. The design used for the research is quantitative and correlational. The analytical instrument used is the engineering sustainability map, which contains the learning outcomes related to sustainability that are expected of engineering students upon completion of their studies. The methodology is used to analyze the curricula of the ten engineering degrees in order to identify what learning outcomes of the engineering sustainability map are developed in each degree. The results indicate that the sustainability competency least present in all the degrees is the “participation in community processes that promotes sustainability,” with an average presence of 23.3%, while the most present is the “application of ethical principles related to the values of sustainability in personal and professional behavior,” with an average presence of 76.6%. In general, learning outcomes related to sustainability have an average presence of 52.1%, so practically half of the cells in the ten engineering sustainability maps are not developed in the degrees under study

Opposing effects on vascular smooth muscle cell proliferation and macrophage-induced inflammation reveal a protective role for the proresolving lipid mediator receptor ChemR23 in intimal hyperplasia

Intimal hyperplasia remains a significant clinical problem in for example coronary artery bypass graft failure. Since omega-3 fatty acids reduce intimal hyperplasia, we hypothesized that the G protein-coupled receptor ChemR23 for the omega-3-derived pro-resolving lipid mediator resolvin E1 drives those effects. ChemR23+/+ and ChemR23-/- mice were generated with or without introduction of the Caenorhabditis elegans fat-1 transgene, which leads to an endogenous omega-3 fatty acid synthesis and thus increasing the substrate for resolvin E1 formation. ChemR23 deletion significantly increased intimal hyperplasia 28 days after ligation of the left common carotid artery. Mice expressing the fat-1 transgene showed reduced intimal hyperplasia independently of ChemR23 expression. ChemR23-/- Vascular smooth muscle cells (VSMCs) exhibited a significantly lower proliferation compared with VSMCs derived from ChemR23+/+ mice. In contrast, ChemR23-/- peritoneal macrophages had significantly higher mRNA levels of pro-inflammatory cytokines compared with ChemR23+/+ macrophages. Finally, conditioned media (CM) transfer from ChemR23-/- macrophages to VSMCs significantly increased VSMC proliferation compared with CM from ChemR23+/+ macrophages. Taken together, these results point to a dual effect of ChemR23 in resolution pharmacology by directly stimulating VSMC proliferation and at the same time suppressing macrophage-induced VSMC proliferation. In conclusion, these differential effects of ChemR23 signaling in VSMC and macrophages open up a novel notion for intimal hyperplasia pathophysiology, where ChemR23-transduced effects on the vascular wall may vary, and even be opposing, depending on the degrees of resolution of inflammation

R+D+I

Concurs d’idees per a l'ordenació dels Sectors Can Banús i Castell de MogodaFinalistaPeer ReviewedPostprint (published version

Spatially explicit analysis reveals complex human genetic gradients in the Iberian Peninsula

The Iberian Peninsula is a well-delimited geographic region with a rich and complex human history. However, the causes of its genetic structure and past migratory dynamics are not yet fully understood. In order to shed light on them, here we evaluated the gene flow and genetic structure throughout the Iberian Peninsula with spatially explicit modelling applied to a georeferenced genetic dataset composed of genome-wide SNPs from 746 individuals belonging to 17 different regions of the Peninsula. We found contrasting patterns of genetic structure throughout Iberia. In particular, we identified strong patterns of genetic differentiation caused by relevant barriers to gene flow in northern regions and, on the other hand, a large genetic similarity in central and southern regions. In addition, our results showed a preferential north to south migratory dynamics and suggest a sex-biased dispersal in Mediterranean and southern regions. The estimated genetic patterns did not fit with the geographical relief of the Iberian landscape and they rather seem to follow political and linguistic territorial boundaries.Fundação para a Ciência e a Tecnologia | Ref. POCI-01-0145-FEDER-007274Fundação para a Ciência e a Tecnologia | Ref. SFRH/BD/97200/2013Fundação para a Ciência e a Tecnologia | Ref. IF/01262/2014Ministerio de Economía | Ref. RYC-2015-18241Ministerio de Economía | Ref. MDM-2014-0370Ministerio de Economía y Competitividad | Ref. CGL2016-75389-

...+Prat

Concurs per a l'ordenació del Centre Direccional al Prat NordMencióPeer ReviewedPostprint (published version

Com transformar una esquinçada en cremallera

Concurs d'ordenació del sector "Soterrament de la via fèrria" a MontmelóFinalistaPeer ReviewedPostprint (published version

Mar i muntanya

Concurs per al desenvolupament de l’Eixample Nord de Vilanova i la GeltrúSegon premiPeer ReviewedAward-winningPostprint (published version