ABSTRACT
BACKGROUND: The extracellular matrix (ECM) is a complex tridimensional scaffold that actively participates in physiological and pathological events. The objective of this study was to test whether structural proteins of the ECM and glycosaminoglycans (GAGs) may favor the retention of human apolipoprotein A-I (apoA-I) variants associated with amyloidosis and atherosclerosis. METHODS: Biopolymeric matrices containing collagen type I (Col, a main macromolecular component of the ECM) with or without heparin (Hep, a model of GAGs) were constructed and characterized, and used to compare the binding of apoA-I having the native sequence (Wt) or Arg173Pro, a natural variant inducing cardiac amyloidosis. Protein binding was observed by fluorescence microscopy and unbound proteins quantified by a colorimetric assay. RESULTS: Both, Wt and Arg173Pro bound to the scaffolds containing Col, but the presence of Hep diminished the binding efficiency. Col-Hep matrices retained Arg173Pro more than the Wt. The retained protein was only partially removed from the matrices with saline solutions, indicating that electrostatic interactions may occur but are not the main driving force. Using in addition thermodynamic molecular simulations and size exclusion chromatography approaches, we suggest that the binding of apoA-I variants to the biopolymeric matrices is driven by many low affinity interactions. CONCLUSIONS: Under this scenario Col-Hep scaffolds contribute to the binding of Arg173Pro, as a cooperative platform which could modify the native protein conformation affecting protein folding. GENERAL SIGNIFICANCE: We show that the composition of the ECM is key to the protein retention, and well characterized biosynthetic matrices offer an invaluable in vitro model to mimic the hallmark of pathologies with interstitial infiltration such as cardiac amyloidosis.
Subject(s)
Amyloidosis , Heparin , Humans , Amyloidosis/metabolism , Apolipoprotein A-I/genetics , Apolipoprotein A-I/chemistry , Collagen/metabolism , Extracellular Matrix/metabolism , Heparin/metabolismABSTRACT
El siguiente trabajo de investigación se propone detectar la estructura de funcionamiento de los mercados, la estructura interna y de poder en las organizaciones de comerciantes y la posibilidad de la Alcaldia de aprovechar la misma para mejorar las condiciones de venta, sin afectar negativamente los intereses de los distintos grupos que en ella actúan
Subject(s)
Food , Commerce , Consultants , Bolivia , Cities , Hygiene/education , Research , Market Sanitation , Health Care Sector/standardsABSTRACT
La zona del estudio es una región interandina de difícil acceso, aislada y con malas vías de comunicación. Además se caracteriza por una fuerte resistencia de las foemas culturales y de organización social. Es necesario la participación de organismos de cooperación internacional en la solución de los problemas de salud en estas regiones de Bolivia, país con el más bajo presupuesto percápite en salud de América Latina
