Role of PCSK9 in the course of ejection fraction change after ST-segment elevation myocardial infarction : a pilot study

Altres ajuts: Conselleria d'Educació, Investigació, Cultura i Esport GV/2018/116Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma low-density lipoprotein cholesterol. Beyond lipid control, recent findings suggest a deleterious effect of this protein in the pathogenesis of postmyocardial infarction left ventricle remodelling and heart failure-related complications. The aim of this study was to assess the relationship between circulating PCSK9 and 6 month cardiac magnetic resonance imaging-derived left ventricular ejection fraction (LVEF) after a first ST-segment elevation myocardial infarction (STEMI). We prospectively evaluated 40 patients with a first STEMI, LVEF < 50% and treated with primary percutaneous coronary intervention in which PCSK9 was measured 24 h postreperfusion. All patients underwent cardiac magnetic resonance imaging 1 week and 6 months after STEMI. Baseline characteristics were compared across median values of PCSK9. The association between PCSK9 levels and LVEF at 6 months was evaluated by analysis of covariance. The mean age of the sample was 60 ± 12 years and 33 (82.5%) were male patients. The infarct location was anterior in 27 patients (67.5%), and 9 patients (22.5%) were Killip class ≥ II. The mean 1 week and 6 month LVEF were 41 ± 7% and 48 ± 10%, respectively. The mean PCSK9 was 1.93 ± 0.38 U/mL. Testing the association between serum PCSK9 and 6 month LVEF with analysis of covariance revealed an inverse relationship (r = −0.35, P = 0.028). After multivariate adjustment, circulating PCSK9 remained significant and inversely associated with 6 month LVEF (P = 0.002). In patients with a first STEMI with reduced ejection fraction at index admission and treated with primary percutaneous coronary intervention, circulating PCSK9 was associated with lower LVEF at 6 months

Conformational and thermal characterization of left ventricle remodeling post-myocardial infarction

Adverse cardiac remodeling after myocardial infarction (MI) causes impaired ventricular function and heart failure. Histopathological characterization is commonly used to detect the location, size and shape of MI sites. However, the information about chemical composition, physical structure and molecular mobility of peri- and infarct zones post-MI is rather limited. The main objective of this work was to explore the spatiotemporal biochemical and biophysical alterations of key cardiac components post-MI. The FTIR spectra of healthy and remote myocardial tissue shows amides A, I, II and III associated with proteins in freeze-died tissue as major absorptions bands. In infarcted myocardium, the spectrum of these main absorptions was deeply altered. FITR evidenced an increase of the amide A band and the distinct feature of the collagen specific absorption band at 1338cm-1 in the infarct area at 21days post-MI. At 21days post-MI, it also appears an important shift of amide I from 1646cm-1 to 1637cm-1 that suggests the predominance of the triple helical conformation in the proteins. The new spectra bands also indicate an increase in proteoglycans, residues of carbohydrates in proteins and polysaccharides in ischemic areas. Thermal analysis indicates a deep increase of unfreezable water/freezable water in peri- and infarcted tissues. In infarcted tissue is evidenced the impairment of myofibrillar proteins thermal profile and the emergence of a new structure. In conclusion, our results indicate a profound evolution of protein secondary structures in association with collagen deposition and reorganization of water involved in the scar maturation of peri- and infarct zones post-MI

Capiteles sevillanos. Técnicas avanzadas para su documentación gráfica.

Recent developments in the field of documentation of cultural heritage using digital photogrammetry and scanning have led to a renewed interest in techniques and processes that are being used to get geometric models of heritage. So far, however, there has been little discussion about the definition of standardized processes in order to ensure homogeneity and interoperability. On the other hand, very valuable information of the buildings is contained by capitals. The aim of our research is to get a protocol in the documentation of this kind of architectural elements, through the use and comparison of new technologies in the graphic documentation. For this purpose, we have used photogrammetric techniques and optical scanners in order to obtain field data, specialized software management and modeling point clouds for the development of textured 3D models and graphic design software that allows us to analyze and disseminate the result

Deep Learning Analyses to Delineate the Molecular Remodeling Process after Myocardial Infarction

Specific proteins and processes have been identified in post-myocardial infarction (MI) pathological remodeling, but a comprehensive understanding of the complete molecular evolution is lacking. We generated microarray data from swine heart biopsies at baseline and 6, 30, and 45 days after infarction to feed machine-learning algorithms. We cross-validated the results using available clinical and experimental information. MI progression was accompanied by the regulation of adipogenesis, fatty acid metabolism, and epithelial-mesenchymal transition. The infarct core region was enriched in processes related to muscle contraction and membrane depolarization. Angiogenesis was among the first morphogenic responses detected as being sustained over time, but other processes suggesting post-ischemic recapitulation of embryogenic processes were also observed. Finally, protein-triggering analysis established the key genes mediating each process at each time point, as well as the complete adverse remodeling response. We modeled the behaviors of these genes, generating a description of the integrative mechanism of action for MI progression. This mechanistic analysis overlapped at different time points; the common pathways between the source proteins and cardiac remodeling involved IGF1R, RAF1, KPCA, JUN, and PTN11 as modulators. Thus, our data delineate a structured and comprehensive picture of the molecular remodeling process, identify new potential biomarkers or therapeutic targets, and establish therapeutic windows during disease progression

Determinación del gasto energético (ge) por el método factorial en patinadores cubanos de velocidad

Se estudiaron 4 varones y 5 hembras  del equipo cubano de patinaje velocidad para estimar su estado nutricional, GE y establecer recomendaciones nutricionales. Un microciclo tipo de las etapas de preparación general (G) y especial (E) constituyó el marco de medición. El GE se determinó mediante método factorial. Se realizó estadística  inferencial para considerar diferencias entre variables por  sexo y etapas para p ≤ 0,05. Para calcular las recomendaciones nutricionales se estimó  el NAF. Se observaron características morfológicas similares a las reportadas en patinadores colombianos,  así como un IMC adecuado. El GE por entrenamiento fue significativamente diferente en las dos etapas y el GET fue superior en la de PG. Energéticamente, se observó tendencia a valores superiores en los hombres en todos los indicadores, excepto para las actividades discrecionales durante la etapa de PE y el NAF de ambas y las recomendaciones dependieron de la etapa de preparación de estos patinadores.   Palabras clave: Patinaje velocidad, gasto energético, método factorial, nivel de actividad física (NAF),  índice de masa corporal (IMC).  <br /

Head-to-head comparison of two engineered cardiac grafts for myocardial repair: From scaffold characterization to pre-clinical testing

Cardiac tissue engineering, which combines cells and supportive scaffolds, is an emerging treatment for restoring cardiac function after myocardial infarction (MI), although, the optimal construct remains a challenge. We developed two engineered cardiac grafts, based on decellularized scaffolds from myocardial and pericardial tissues and repopulated them with adipose tissue mesenchymal stem cells (ATMSCs). The structure, macromechanical and micromechanical scaffold properties were preserved upon the decellularization and recellularization processes, except for recellularized myocardium micromechanics that was ∼2-fold stiffer than native tissue and decellularized scaffolds. Proteome characterization of the two acellular matrices showed enrichment of matrisome proteins and major cardiac extracellular matrix components, considerably higher for the recellularized pericardium. Moreover, the pericardial scaffold demonstrated better cell penetrance and retention, as well as a bigger pore size. Both engineered cardiac grafts were further evaluated in pre-clinical MI swine models. Forty days after graft implantation, swine treated with the engineered cardiac grafts showed significant ventricular function recovery. Irrespective of the scaffold origin or cell recolonization, all scaffolds integrated with the underlying myocardium and showed signs of neovascularization and nerve sprouting. Collectively, engineered cardiac grafts -with pericardial or myocardial scaffolds- were effective in restoring cardiac function post-MI, and pericardial scaffolds showed better structural integrity and recolonization capability

Deep Learning Analyses to Delineate the Molecular Remodeling Process after Myocardial Infarction

Specific proteins and processes have been identified in post-myocardial infarction (MI) pathological remodeling, but a comprehensive understanding of the complete molecular evolution is lacking. We generated microarray data from swine heart biopsies at baseline and 6, 30, and 45 days after infarction to feed machine-learning algorithms. We cross-validated the results using available clinical and experimental information. MI progression was accompanied by the regulation of adipogenesis, fatty acid metabolism, and epithelial-mesenchymal transition. The infarct core region was enriched in processes related to muscle contraction and membrane depolarization. Angiogenesis was among the first morphogenic responses detected as being sustained over time, but other processes suggesting post-ischemic recapitulation of embryogenic processes were also observed. Finally, protein-triggering analysis established the key genes mediating each process at each time point, as well as the complete adverse remodeling response. We modeled the behaviors of these genes, generating a description of the integrative mechanism of action for MI progression. This mechanistic analysis overlapped at different time points; the common pathways between the source proteins and cardiac remodeling involved IGF1R, RAF1, KPCA, JUN, and PTN11 as modulators. Thus, our data delineate a structured and comprehensive picture of the molecular remodeling process, identify new potential biomarkers or therapeutic targets, and establish therapeutic windows during disease progression

Low-density lipoprotein receptor-related protein 1 deficiency in cardiomyocytes reduces susceptibility to insulin resistance and obesity

Background: Low-density lipoprotein receptor-related protein 1 (LRP1) plays a key role in fatty acid metabolism and glucose homeostasis. In the context of dyslipemia, LRP1 is upregulated in the heart. Our aim was to evaluate the impact of cardiomyocyte LRP1 deficiency on high fat diet (HFD)-induced cardiac and metabolic alterations, and to explore the potential mechanisms involved. Methods: We used TnT-iCre transgenic mice with thoroughly tested suitability to delete genes exclusively in cardiomyocytes to generate an experimental mouse model with conditional Lrp1 deficiency in cardiomyocytes (TNT-iCre+-LRP1flox/flox). Findings: Mice with Lrp1-deficient cardiomyocytes (cm-Lrp1-/-) have a normal cardiac function combined with a favorable metabolic phenotype against HFD-induced glucose intolerance and obesity. Glucose intolerance protection was linked to higher hepatic fatty acid oxidation (FAO), lower liver steatosis and increased whole-body energy expenditure. Proteomic studies of the heart revealed decreased levels of cardiac pro-atrial natriuretic peptide (pro-ANP), which was parallel to higher ANP circulating levels. cm-Lrp1-/- mice showed ANP signaling activation that was linked to increased fatty acid (FA) uptake and increased AMPK/ ACC phosphorylation in the liver. Natriuretic peptide receptor A (NPR-A) antagonist completely abolished ANP signaling and metabolic protection in cm-Lrp1-/- mice. Conclusions: These results indicate that an ANP-dependent axis controlled by cardiac LRP1 levels modulates AMPK activity in the liver, energy homeostasis and whole-body metabolism

IVRA: Romanas, visigodas y bizantinas. Una experiencia de innovación docente en clave de género

La experiencia que se presenta pretende, por un lado, cubrir la necesidad de crear unos materiales docentes en los que la transversalidad, la interdisciplinariedad y las competencias de género y ciudadanía fueran su hilo conductor con la finalidad de que se pudieran utilizar en los estudios jurídicos y, en especial, en el marco de las asignaturas relacionadas con el Derecho Romano. Por otra parte, pretende ser una experiencia en innovación docente, que ha derivado en la realización de investigación científica sobre la materia.  Todo ello se ha llevado a cabo por un grupo esencialmente de profesoras de carácter interuniversitario y multidisciplinar. Además, la transferencia de resultados obtenidos ha sobrepasado el ámbito universitario para llegar a la sociedad en general.

Ivra: Romanas, visigodas y bizantinas. Una experiencia de innovación docente en clave de género

La experiencia que se presenta pretende, por un lado, cubrir la necesidad de crear unos materiales docentes en los que la transversalidad, la interdisciplinariedad y las competencias de género y ciudadanía fueran su hilo conductor con la finalidad de que se pudieran utilizar en los estudios jurídicos y, en especial, en el marco de las asignaturas relacionadas con el Derecho Romano. Por otra parte, pretende ser una experiencia en innovación docente, que ha derivado en la realización de investigación científica sobre la materia. Todo ello se ha llevado a cabo por un grupo esencialmente de profesoras de carácter interuniversitario y multidisciplinar. Además, la transferencia de resultados obtenidos ha sobrepasado el ámbito universitario para llegar a la sociedad en genera