0000000000526164
AUTHOR
Federico Mayor
Beta-blockers: Historical Perspective and Mechanisms of Action
Beta-blockers are widely used molecules that are able to antagonize β-adrenergic receptors (ARs), which belong to the G protein-coupled receptor family and receive their stimulus from endogenous catecholamines. Upon β-AR stimulation, numerous intracellular cascades are activated, ultimately leading to cardiac contraction or vascular dilation, depending on the relevant subtype and their location. Three subtypes have been described that are differentially expressed in the body (β1-, β2- and β3-ARs), β1 being the most abundant subtype in the heart. Since their discovery, β-ARs have become an important target to fight cardiovascular disease. In fact, since their discovery by James Black in the …
Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2
Tumor vessel dysfunction is a pivotal event in cancer progression. Using an in vivo neovascularization model, we identified G protein–coupled receptor kinase 2 (GRK2) as a key angiogenesis regulator. An impaired angiogenic response involving immature vessels was observed in mice hemizygous for Grk2 or in animals with endothelium-specific Grk2 silencing. ECs isolated from these animals displayed intrinsic alterations in migration, TGF-β signaling, and formation of tubular networks. Remarkably, an altered pattern of vessel growth and maturation was detected in postnatal retinas from endothelium-specific Grk2 knockout animals. Mouse embryos with systemic or endothelium-selective Grk2 ablation …
Bloqueadores beta: perspectiva histórica y mecanismos de acción
Resumen Los bloqueadores beta son moleculas ampliamente utilizadas y capaces de antagonizar los receptores adrenergicos (RA) beta, pertenecen a la familia de receptores acoplados a proteinas G y reciben el estimulo de las catecolaminas endogenas. Tras su estimulacion, se activan cascadas intracelulares que en ultima instancia originan la contraccion cardiaca o la dilatacion vascular, segun el subtipo y su ubicacion. Se han descrito 3 subtipos, que se expresan de manera diferenciada en el organismo (RA-β1, β2 y β3), y el subtipo β1 es el mas abundante en el corazon. Desde su descubrimiento, los RA-β se han convertido en diana para combatir las enfermedades cardiovasculares. Desde su invencio…