Linking In Vitro Models of Endothelial Dysfunction with Cell Senescence

Disfunció endotelial; Envellliment cel·lularDisfunción endotelial; Envejecimiento celularEndothelial dysfunction; SenescenceEndothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel pharmacological therapies. We subjected human umbilical vein endothelial cells (HUVECs) to different periods of nutrient deprivation or increasing doses of H2O2 to represent starvation or elevated oxidative stress, respectively, to investigate changes in cellular function. Both in vitro cellular models of endothelial cell dysfunction-associated senescence developed in this study, starvation and oxidative stress, were validated by markers of cellular senescence (increase in β-galactosidase activity, and changes in senescence gene markers SIRT1 and P21) and endothelial dysfunction as denoted by reductions in angiogenic and migratory capabilities. HUVECs showed a significant H2O2 concentration-dependent reduction in cell viability (p < 0.0001), and a significant increase in oxidative stress (p < 0.0001). Furthermore, HUVECs subjected to 96 h of starvation, or exposed to concentrations of H2O2 of 400 to 1000 μM resulted in impaired angiogenic and migratory potentials. These models will enable improved physiological studies of endothelial cell dysfunction, and the rapid testing of cellular efficacy and toxicity of future novel therapeutic compounds.This research was funded by Beca de Investigacion Basica en Cardiologia from the Sociedad Española de Cardiologia, Fondo de Investigacion en Salud (grants PI18/00277, PI16/00742, PI19/00264, PI18/00960 and PI15/00553) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional (FEDER), and Spanish Society of Respiratory Medicine (SEPAR) and Catalan Society of Pneumology (SOCAP) grants. FRJT and OTC are the recipients of the Ayudas para la formación de profesorado universitario (FPU19/04925) and Miguel Servet (CP17/00114) grants, respectively, from the Spanish Ministry of Science and Innovation. IDIBAPS belongs to the CERCA Programme, and receives partial funding from the Generalitat de Catalunya. Cofunding was provided by the Fondo Europeo de Desarrollo Regional (FEDER); “Una manera de hacer Europa”

Intracoronary administration of allogeneic adipose tissue-derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function, in a translational model of acute myocardial infarction

Background-¿Autologous adipose tissue-derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post-myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long-term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. Methods and Results-¿Thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated, n=10; ATMSCs-treated, n=9) or long term (60 days after acute myocardial infarction vehicle-treated, n=7; ATMSCs-treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs-treated animals (48.6 6% versus 55.9 5.7% in vehicle; P=0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor, granulocyte macrophage colony-stimulating factor, and stromal-derived factor-1a gene expression; and increased M2 macrophages (67.2 10% versus 54.7 10.2% in vehicle; P=0.016). In long-term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in ATMSCs-treated animals, compared to vehicle (87.9 28.7 versus 57.4 17.7 mL/min per gram at 7 days; P=0.034 and 99 22.6 versus 43.3 14.7 22.6 mL/min per gram at 60 days; P=0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs-treated animals (118 18 versus 92.4 24.3 vessels/mm2 in vehicle; P=0.045). Cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. Conclusions-¿In this porcine acute myocardial infarction model, allogeneic ATMSCs-based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance-measured perfusion. No effect on left ventricular volumes or ejection fraction was observed

Col·leccions singulars a les biblioteques de la Universitat Autònoma de Barcelona

Les biblioteques de la Universitat Autònoma de Barcelona són, com la mateixa institució, entitats amb una història curta; però, malgrat que van començar la seva activitat fa menys de cinquanta anys, els seus fons han assolit una importància considerable i superen en quantitat els de moltes universitats centenàries del nostre context. Les col·leccions de fons antics de les biblioteques de la UAB són, per aquesta mateixa raó, limitades, si bé se n'han anat creant algunes d'especialitzades d'importància i valor singulars. Aquest llibre pretén donar-les a conèixer al món universitari, però també al públic en general. Moltes són col·leccions úniques, fruit del treball persistent del personal bibliotecari, del professorat i de la generositat de moltes persones particulars, que han donat o llegat a la nostra universitat els seus arxius, les seves biblioteques personals o les seves col·leccions especialitzades. Aquestes col·leccions comprenen molts àmbits de les ciències i de les humanitats i, molt sovint, es tracta de col·leccions úniques al nostre país. Hi trobareu també un ampli ventall de tipologies documentals en llengües diverses, des dels mapes fins als audiovisuals, des de les revistes i diaris fins als cartells, des dels fons antics fins als més actuals, arxius personals i fons institucionals. Les biblioteques de la Universitat, a més d'inventariar i catalogar aquests fons documentals, també porten a terme una tasca constant de preservació i difusió, que sovint inclou la digitalització dels documents, que després es posen a l'abast del públic general mitjançant el dipòsit digital institucional (ddd.uab.cat)

Regulator of calcineurin 1 mediates pathological vascular wall remodeling

Angiotensin-II–driven calcineurin activation and regulator of calcineurin-1 (Rcan-1) expression is required for pathological vascular remodeling in mice

Identificació dels mecanismes d'inflamació i proliferació cel·lular implicats en la restenosi

[cat] DELIMITACIÓ DELS OBJECTIUS I HIPÒTESI DE TREBALL:La restenosi és la limitació més important de l'èxit a llarg termini dels procediments de revascularització coronària percutània. OBJECTIU: Desenvolupar un model de restenosi en el ratolí que ens permeti l'estudi dels mecanismes moleculars i cel.lulars implicats en el desenvolupament d'hiperplàsia intimal, mitjançant la seva aplicació a models murins genèticament modificats. La hipòtesi general de l'estudi és que la interferència a diferents nivells en l'activació dels mecanismes inflamatoris i de proliferació cel.lular que es produeix com a conseqüència d'una lesió arterial, com en el cas de l'intervencionisme coronari percutani, pot prevenir el desenvolupament d'hiperplàsia intimal. ADEQUACIÓ DEL MÈTODE ALS OBJECTIUS PLANTEJATS:S'ha aplicat un mètode de denudació endotelial de l'artèria femoral en el ratolí que resulta en una adequada formació d'hiperplàsia intimal. Emprant aquest model s'ha analitzat l'efecte de l'absència del regulador del cicle cel.lular p27, del receptor de MCP-1, CCR2, i dels fàrmacs rapamicina i sulindac sobre la formació d'hiperplàsia intimal. JUDICI PONDERAT DE LES APLICACIONS DE LA TESI:1. En conjunt, aquest projecte representa la integració de la enginyeria genètica, representada en els models murins d'aterosclerosi i de modulació del cicle cel.lular i els mecanismes de resposta a la lesió arterial. A la llum dels resultats d'aquesta tesi, el més probable és que el control de la restenosi s'aconsegueixi mitjançant estratègies que abarquin vàries de les diverses vies implicades en aquest procés multifactorial. Els resultats derivats d'aquestes investigacions poden portar al desenvolupament d'estratègies terapèutiques de prevenció de restenosi post-intervencionisme coronari. PUBLICACIONS:- Mercè Roqué, John T. Fallon, Juan J. Badimón, Wen X. Zhang, Mark B. Taubman, Ernane D. Reis. Mouse model of femoral artery denudation injury associated with the rapid accumulation of adhesion molecules on the luminal surface and recruitment of neutrophils. Arterioscler Thromb Vasc Biol 2000;20:335-342.- Ernane D. Reis, Mercè Roqué, Carlos Cordón-Cardó, Marija Drobnjak, Valentin Fuster, Juan J. Badimón. Apoptosis, proliferation, and p27 expression during vessel wall healing: Time course study in a mouse model of transluminal femoral artery injury. J Vasc Surg 2000;32:1022-1029.- Mercè Roqué, Ernane D. Reis, Carlos Cordón-Cardó, Mark B. Taubman, John T. Fallon, Valentin Fuster, Juan J. Badimón. Effect of p27 deficiency and rapamycin on intimal hyperplasia: In vivo and in vitro studies using a p27 knockout mouse model. Lab Invest 2001;81:895-903. - Mercè Roqué, William J. H. Kim, Michaela Gazdoin, Alia Malik, Ernane D. Reis, John T. Fallon, Juan J. Badimón, Israel F. Charo, Mark B. Taubman. CCR2 deficiency decreases intimal hyperplasia after arterial injury. Arterioscler Thromb Vasc Biol 2002;22:554-559. - Ernane D. Reis, Mercé Roqué, Hayes Dansky, John T. Fallon, Juan J. Badimón, Carlos Cordón-Cardó, Steven J. Shiff, Edward A. Fisher. Sulindac inhibits neointimal formation after arterial injury in wild-type and apolipoprotein E-deficient mice. Proc Natl Acad Sci U.S.A. 2000;97:12764-12769.[eng] "STUDY OF MECHANISMS OF INFLAMMATION AND CELL PROLIFERATION INVOLVED IN RESTENOSIS USING A MURINE MODEL OF INTIMAL HYPERPLASIA"Restenosis is the limiting factor in long-term success of percutaneous coronary interventions. The aim of the thesis was to develop a model of intimal hyperplasia in the mouse that allows the study of the mechanisms of inflammation and proliferation involved in restenosis development by using genetically altered mouse models. The general hypothesis of the thesis is that interfering at differents levels of activation of the mechanisms involved in the response-to-arterial injury will prevent the development of intimal hyperplasia.Methods: A model of transluminal endothelial denudation to the mouse femoral artery has been implemented, resulting in an adequate formation of intimal hyperplasia. Using this model, the effect of the absence of the cell-cycle regulator p27, MCP-1 receptor, CCR2, and the drugs rapamycin and sulindac, on intimal hyperplasia formation, has been analyzed.Together, the results of this investigations may bring additional insight on the mechanisms leading to intimal hyperplasia and help in developing new therapeutic strategies for preventing restenosis after percutaneous coronary interventions

Fibrous Platinum-Group Minerals in “Floating Chromitites” from the Loma Larga Ni-Laterite Deposit, Dominican Republic

This contribution reports on the observation of enigmatic fibrous platinum-group minerals (PGM) found within a chromitite body included in limonite (“floating chromitite”) from Ni-laterites in the Dominican Republic. Fibrous PGM have a Ru-Os-Ir-Fe dominated composition and are characterized by fibrous textures explained by grain-forming fibers which are significantly longer (1–5 µm) than they are wide (~100 nm). Back-scattered electron (BSE) images suggest that these nanofibers are platinum-group elements (PGE)-bearing and form &lt;5 µm thick layers of bundles which are oriented orthogonal to grains’ surfaces. Trace amounts of Si are most likely associated with PGE-bearing nanofibers. One characteristic fibrous PGM was studied in detail: XRD analyses point to ruthenian hexaferrum. However, the unpolished fibrous PGM shows numerous complex textures on its surface which are suggestive for neoformation processes: (i) features suggesting growth of PGE-bearing nanofibers; (ii) occurrence of PGM nanoparticles within film material (biofilm?) associated with PGE-bearing nanofibers; (iii) a Si-rich and crater-like texture hosting PGM nanoparticles and an Ir-rich accumulation of irregular shape; (iv) complex PGM nanoparticles with ragged morphologies, resembling sponge spicules and (v) oval forms (&lt;1 µm in diameter) with included PGM nanoparticles, similar to those observed in experiments with PGE-reducing bacteria. Fibrous PGM found in the limonite may have formed due to supergene (bio-)weathering of fibrous Mg-silicates which were incorporated into desulphurized laurite during stages of serpentinization

Efficacy of radial extracorporeal shock wave therapy compared with botulinum toxin type A injection in treatment of lower extremity spasticity in subjects with cerebral palsy: A randomized, controlled, cross-over study

Objectives: To investigate whether botulinum toxin type A (BTX-A) injection is more effective than radial extracorporeal shock wave therapy in reducing plantar flexor muscle spasticity in subjects with cerebral palsy. Methods: A total of 68 subjects with cerebral palsy were randomly allocated to BTX-A injection (Group 1) or radial extracorporeal shock wave therapy (Group 2) (first experiment; E1). Outcome was evaluated using the Tardieu V1 and V3 stretches, at 3 weeks, 2 months (M2) and M3 after baseline. At M6 subjects in Group 1 received radial extracorporeal shock wave therapy and subjects in Group 2 received BTX-A injection (second experiment; E2); outcome was evaluated as in E1. Treatment success was defined as improvement in foot dorsiflexion ≥10° when performing the V3 stretch at M2 in both experiments. Results: In both experiments mean V1 and V3 significantly improved over time. In E1 both treatments resulted in similar treatment success. In E2 fewer subjects treated with BTX-A injection reached the criteria of treatment success than did subjects treated with radial extracorporeal shock wave therapy, which was due to a carry-over effect from E1. No significant complications were observed. Conclusion: BTX-A injection is not superior to radial extracorporeal shock wave therapy in the treatment of plantar flexor muscle spasticity in subjects with cerebral palsy