El dermatán sulfato : una nueva estrategia para el diagnóstico y tratamiento de la injuria vascular
Atherosclerosis is a chronic inflammatory disease triggered by the interaction of several genetic factors with external stimuli. The activation and dysfunction of the vascular endothelium is one of the main links between exposure to risk factors and the development of atherosclerosis. The qualitativ...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2019
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2902 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2902.dir/2902.PDF |
| Aporte de: |
| Sumario: | Atherosclerosis is a chronic inflammatory disease triggered by the interaction of several genetic factors with external stimuli. The activation and dysfunction of the vascular endothelium is one of the main links between exposure to risk factors and the development of atherosclerosis. The qualitative and quantitative modifications of the vascular extracellular matrix (vECM) are an early manifestation of endothelial activation. It has been previously described that the sulfation and elongation pattern of the glycosaminoglycans chondroitin sulfate and dermatan sulfate are modified in atherogenesis. The polyelectrolyte complexes (PECs) that have glycosaminoglycans in their composition may be new platforms for the diagnosis and treatment of vascular disease. Results from this thesis show that the glycosaminoglycan low molecular weight dermatan sulfate (LMMDS) modulates the early events of atherogenesis, stimulating cell proliferation, vECM remodeling and cell migration, in a non-inflammatory microenvironment. Moreover, this thesis demonstrates that the ionotropic gelification between the polymers LMMDS and chitosan produces stable nanometric PECs. This system offers a unique combination of biologic characteristics, such as its binding to endothelial cells in culture and the subsequent modulation of the early stages of angiogenesis. PECs made with LMMDS constitute a novel platform towards the implementation of new strategies to prevent, diagnose and treat many cardiovascular diseases. |
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