Pathological vascular remodeling is the underlying cause of atherosclerosis and abdominal aortic aneurysm (AAA). Here, we analyzed the role of galectin-1 (Gal-1), a β-galactoside-binding protein, as ...a therapeutic target for atherosclerosis and AAA. Mice lacking Gal-1 (
) developed severe atherosclerosis induced by pAAV/D377Y-mPCSK9 adenovirus and displayed higher lipid levels and lower expression of contractile markers of vascular smooth muscle cells (VSMCs) in plaques than wild-type mice. Proteomic analysis of
aortas showed changes in markers of VSMC phenotypic switch and altered composition of mitochondrial proteins. Mechanistically, Gal-1 silencing resulted in increased foam cell formation and mitochondrial dysfunction in VSMCs, while treatment with recombinant Gal-1 (rGal-1) prevented these effects. Furthermore, rGal-1 treatment attenuated atherosclerosis and elastase-induced AAA, leading to higher contractile VSMCs in aortic tissues. Gal-1 expression decreased in human atheroma and AAA compared to control tissue. Thus, Gal-1-driven circuits emerge as potential therapeutic strategies in atherosclerosis and AAA.
The conformational properties of the C-glycosyl analogue of the core trisaccharide α-d-Man-(1 → 3)-α-d-Man-(1 → 6)-d-Man in solution have been carefully analyzed by a combination of NMR spectroscopy ...and time-averaged restrained molecular dynamics. It has been found that both the α-1,3- and the α-1,6-glycosidic linkages show a major conformational averaging. Unusual Φ ca. 60° orientations for both Φ torsion angles are found. Moreover, a major conformational distinction between the natural compound and the glycomimetic affects to the behavior of the ω16 torsion angle around the α-1 → 6-linkage. Despite this increased flexibility, the C-glycosyl analogue is recognized by three mannose binding lectins, as shown by NMR (line broadening, TR−NOE, and STD) and surface plasmon resonance (SPR) methods. Moreover, a process of conformational selection takes place, so that these lectins probably bind the glycomimetic similarly to the way they recognize the natural analogue. Depending upon the architecture and extension of the binding site of the lectin, loss or gain of binding affinity with respect to the natural analogue is found.
The development of effective strategies for the synthesis of phosphatidylinositol precursors such as that which contains the trisaccharide 1, the study of their conformational features and dynamics, ...and the investigation of their biological properties may result in a better understanding of the mechanism of signal transduction of insulin and a number of growth factors. This new pathway of intracellular signalling has been postulated to proceed through uncharacterized inositolphosphoglycan mediators containing substructures such as 1.
Comunicación - Educación A., Octavio Henao; Cañellas, Antonio J. Colom; Castro, María Victoria Rodríguez ...
Siglo del Hombre Editores,
2000
eBook, Book
Odprti dostop
En las últimas décadas, diversos sectores de la comunidad científica iberoamericana y de la sociedad en general han venido constatando la importancia de entender diferentes manifestaciones de la ...cultura contemporánea desde la estratégica relación entre la comunicación y la educación. Problemáticas como el conflicto generado entre modelos pedagógicos tradicionales y las transformaciones de las nuevas subjetividades, de las identidades, de la familia, de las tecnologías de la información y la comunicación, forman parte de esos retos de la cultura de nuestros días que pueden ser abordados, en la producción discursiva y en la praxis, a partir de la intersección entre los campos de la comunicación y la educación.
