Inhibitory Effects of LRP1-Based Immunotherapy on Cardiac Extracellular Matrix Biophysical Alterations Induced by Hypercholesterolemia

The accumulation of lipids in cardiomyocytes contributes to cardiac dysfunction. The specific blockage of cardiomyocyte cholesteryl ester (CE) loading by antibodies (Abs) against the P3 sequence (Gly-Cys) of the LRP1 receptor improves cardiac insulin sensitivity. The impact of anti-P3 Abs on high-fat diet (HFD)-induced cardiac extracellular matrix (ECM) biophysical alterations was analyzed. Both IrP (without Abs) and P3-immunized rabbits (with Abs) were randomized into groups fed either HFD or a standard chow diet. Cardiac lipids, proteins, and carbohydrates were characterized by Fourier transform infrared spectroscopy in the attenuated total reflectance mode. The hydric organization and physical structure were determined by differential scanning calorimetry. HFD increased the levels of esterified lipids, collagen, and α-helical structures and upregulated fibrosis, bound water, and ECM plasticization in the heart. The inhibitory effect of anti-P3 Abs on cardiac CE accumulation was sufficient to reduce the collagen-filled extracellular space, the level of fibrosis, and the amount of bound water but did not counteract ECM plasticization in the heart of hypercholesterolemic rabbits.The economic support to develop this project was received from Fundació MARATÓ TV3 with Grant 201521-10 (to V.L.-C.), FIS PI21/01523 (to V.L.-C.) from the Instituto de Salud Carlos III (ISCIII) and co-financed with ERDFs, and Fundación BBVA Ayudas a equipos de investigación 2019. This work was also funded by the Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SECyT-UNC) Grants PROYECTOS CONSOLIDAR 2018–2021 (to G.C.), Fondo para la Investigación Científica y Tecnológica (FONCyT), and Préstamo BID Proyecto de Investigación en Ciencia y Tecnología (PICT) Grants 2015-0807 and 2017-4497 (to G.C.). Support was received from the Albert Renold Travel Fellowship Programme 2019 from the European Foundation of the study of Diabetes (EFSD) and the Wood-Whelan fellowship Programme 2019 from the International Union of Biochemistry and Molecular Biology (IUBMB) to cover the stay of V.A.D. in Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC) and Biomedical Research Institute Sant Pau (IIB Sant Pau). V.A.D. is a postdoctoral fellow of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI). A.B.-A. is a predoctoral fellow (FI19/00205) granted by the Programme _Contratos predoctorales de formación de investigación en salud_ from the Instituto de Salud Carlos III (ISCIII) and co-financed with ERDFs. Our group is part of CIBER Enfermedades Cardiovasculares (CIBERCV; CB16/11/00276 to J.M.G. and V.L.-C.) and CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM; CB07/08/0016 to J.C.E.-G.), projects run by the Instituto de Salud Carlos III. Our group also participates in Redes de investigación (Enfermedades Metabóloicas y Cáncer RED2018-102799-T), a project run by MINECO. The V.L.-C. group is recognized by Generalitat de Catalunya (2017 SGR 946). The authorsd thank Eva Prats and the staff from Centres Científics i Tecnològics de la Universitat de Barcelona (Campus Casanova) (CCiT/UB) for sample processing for electron microscopy. The IR-SANTPAU is a center of CERCA Programme/Generalitat de Catalunya

La inmunoterapia basada en LRP1 como estrategia eficaz para inhibir las alteraciones metabólicas en el sistema cardiovascular

Trabajo presentado en el Congreso SEC de la Salud Cardiovascular, celebrado en Mallorca (España), del 20 al 22 de octubre de 2022Background: Antibodies against the P3 sequence (Gly1127-Cys1140) of LRP1 (anti-P3 Abs) specifically block cholesteryl ester (CE) accumulation in vascular cells. LRP1 is a key regulator of insulin receptor (InsR) trafficking in different cell types. The link between CE accumulation and the insulin response are largely unknown. Here, the effects of P3 peptide immunization on the alterations induced by a high-fat diet (HFD) in cardiac insulin response were evaluated. Methods: Irrelevant (IrP)- or P3 peptide-immunized rabbits were randomized into groups fed either HFD or normal chow. Cardiac lipid content was characterized by thin-layer chromatography, confocal microscopy, and electron microscopy. LRP1, InsR and glucose transporter type 4 (GLUT4) levels were determined in membranes and total lysates from rabbit heart. The interaction between InsR and LRP1 was analyzed by immunoprecipitation and confocal microscopy. Insulin signaling activity and glucose uptake were evaluated in HL-1 cells exposed to rabbit serum from the different groups. Findings: HFD reduces cardiac InsR and GLUT4 membrane levels and the interactions between LRP1/InsR. Targeting the P3 sequence on LRP1 through anti-P3 Abs specifically reduces CE accumulation in the heart independently of changes in the circulating lipid profile. This restores InsR and GLUT4 levels in cardiac membranes as well as the LRP1/InsR interactions of HFD-fed rabbits. In addition, anti-P3 Abs restores the insulin signaling cascade and glucose uptake in HL-1 cells exposed to hypercholesterolemic rabbit serum

Data on New Intermediate and Accidental Hosts Naturally Infected with <i>Angiostrongylus cantonensis</i> in La Gomera and Gran Canaria (Canary Islands, Spain)

Angiostrongylus cantonensis is a metastrongyloid nematode and the etiologic agent of angiostrongyliasis, a disease characterized by eosinophilic meningitis. This emerging zoonotic parasite has undergone great expansion, including in some regions of Europe and America. In the Canary Islands, the parasite was first discovered parasitizing Rattus rattus on the island of Tenerife in 2010. To date, the distribution of this parasite in the Canary Islands has been restricted to the northern zone and the main cities of Tenerife. Using molecular tools for the sentinel species present in the Canary Islands, this study confirmed the presence of the nematode on two other islands in the Canary Archipelago: La Gomera and Gran Canaria. Furthermore, this emerging parasite was detected, besides in the common definitive host R. rattus, in wild Mus musculus and Felis catus and in four terrestrial gastropod species, Limacus flavus, Milax gagates, Insulivitrina emmersoni, and Insulivitrina oromii, two of them endemic to La Gomera, for the first time, increasing the number of non-definitive host species. This study reinforces the expansion character of A. cantonensis and highlights the importance of knowledge about sentinel species for identifying new transmission locations that help prevent and control the transmission of the parasite and, thus, prevent public health problems

Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response

International audienceBackgroundAntibodies against the P3 sequence (Gly1127-Cys1140) of LRP1 (anti-P3 Abs) specifically block cholesteryl ester (CE) accumulation in vascular cells. LRP1 is a key regulator of insulin receptor (InsR) trafficking in different cell types. The link between CE accumulation and the insulin response are largely unknown. Here, the effects of P3 peptide immunization on the alterations induced by a high-fat diet (HFD) in cardiac insulin response were evaluated.MethodsIrrelevant (IrP)- or P3 peptide-immunized rabbits were randomized into groups fed either HFD or normal chow. Cardiac lipid content was characterized by thin-layer chromatography, confocal microscopy, and electron microscopy. LRP1, InsR and glucose transporter type 4 (GLUT4) levels were determined in membranes and total lysates from rabbit heart. The interaction between InsR and LRP1 was analyzed by immunoprecipitation and confocal microscopy. Insulin signaling activity and glucose uptake were evaluated in HL-1 cells exposed to rabbit serum from the different groups.FindingsHFD reduces cardiac InsR and GLUT4 membrane levels and the interactions between LRP1/InsR. Targeting the P3 sequence on LRP1 through anti-P3 Abs specifically reduces CE accumulation in the heart independently of changes in the circulating lipid profile. This restores InsR and GLUT4 levels in cardiac membranes as well as the LRP1/InsR interactions of HFD-fed rabbits. In addition, anti-P3 Abs restores the insulin signaling cascade and glucose uptake in HL-1 cells exposed to hypercholesterolemic rabbit serum

IMPACTS OF CLIMATE CHANGE ON THE NATURAL DISTRIBUTION OF SPECIES OF LOWLAND HIGH AND LOW IN THE AMAZON

ABSTRACT The areas of Amazonian floodplains have added ecological value to their multiple ecosystem services, including water supply, local climate regulation, biodiversity with a marked number of endemic species, and diversity of micro-habitat. Considering the importance of conserving these environments, this study aimed to analyze the behavior and delimit the areas of the natural distribution of forest species Alchornea castaneifolia (Willd.) A. Juss and Laetia corymbulosa (lowland low), Maquira coriacea (H.Karst.) C.C. Berg (Moraceae), and Ocotea cymbarum Kunth (high floodplain), besides evaluating the potential impacts of climate change on the future distribution inferring on its conservation. The potential species distribution was modeled using Environmental Modelling & Software, by employing algorithms such as Bioclim, Domain, Maximum Entropy, Random Forests, and Support Vector Machine (SVM). The projections indicate that climate change threatens the occurrence of floodplain species. Under the SSP 585 scenario for both periods, the four species studied will lose areas of climatic adequacy until the end of the 21st century, especially in the Brazilian Amazon. The study shows the need to increase socio-environmental responsibility through conserving current protected areas in freshwater ecosystems and implementing new priority areas for conserving wetlands (Ramsar Sites) in the Amazon. Such measures are essential to ensure in situ conservation and protect them from habitat loss

Material audiovisual : aprende y juega con las emociones

El trabajo obtuvo un Premio Tomás García Verdejo a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso académico 2015/2016. Modalidad ASe describe una proyecto llevado a cabo en el CEE Antonio Tomillo de Zafra (Badajoz), que consistió en la elaboración de materiales audiovisuales para trabajar las emociones en la educación especial. Se realizaron actividades, dinámicas y juegos para incorporar el uso de la inteligencia emocional y social como una forma positiva, que favorece los procesos de enseñanza-aprendizaje, mejora el bienestar personal y colectivo y las relaciones entre todos los sectores implicados en la educación: el alumnado, el centro y las familiasExtremaduraES

In Vivo Study of Nasal Bone Reconstruction with Collagen, Elastin and Chitosan Membranes in Abstainer and Alcoholic Rats

The aim of the present study was to evaluate the use of collagen, elastin, or chitosan biomaterial for bone reconstruction in rats submitted or not to experimental alcoholism. Wistar male rats were divided into eight groups, submitted to chronic alcohol ingestion (G5 to G8) or not (G1 to G4). Nasal bone defects were filled with clot in animals of G1 and G5 and with collagen, elastin, and chitosan grafts in G2/G6, G3/G7, and G4/G8, respectively. Six weeks after, all specimens underwent radiographic, tomographic, and microscopic evaluations. Bone mineral density was lower in the defect area in alcoholic animals compared to the abstainer animals. Bone neoformation was greater in the abstainer groups receiving the elastin membrane and in abstainer and alcoholic rats receiving the chitosan membrane (15.78 ± 1.19, 27.81 ± 0.91, 47.29 ± 0.97, 42.69 ± 1.52, 13.81 ± 1.60, 18.59 ± 1.37, 16.54 ± 0.89, and 37.06 ± 1.17 in G1 to G8, respectively). In conclusion, osteogenesis and bone density were more expressive after the application of the elastin matrix in abstainer animals and of the chitosan matrix in both abstainer and alcoholic animals. Chronic alcohol ingestion resulted in lower bone formation and greater formation of fibrous connective tissue

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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