Dinámica de los proteoglicanos de la matriz extracelular en la injuria vascular inducida por lipoproteínas ricas en triglicéridos
Atherosclerosis is a spatially nonrandom and temporally nonlinear process that initially\naffects areas of the arterial tree. These areas display a unique dysfunctional endothelial\nphenotype characterized by a pro-inflammatory, pro-thrombotic and angiogenic state.\nAtheroprotective and atheroprone...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2016
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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_1172 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1172.dir/1172.PDF |
| Aporte de: |
| Sumario: | Atherosclerosis is a spatially nonrandom and temporally nonlinear process that initially\naffects areas of the arterial tree. These areas display a unique dysfunctional endothelial\nphenotype characterized by a pro-inflammatory, pro-thrombotic and angiogenic state.\nAtheroprotective and atheroprone endothelial phenotypes are associated with distinct\npatterns of gene expression, signaling pathways, and extracellular matrix (ECM)\nremodeling. The effect of very low density lipoprotein (VLDL) on endothelial function has\nbeen scarcely studied, particularly endothelial ECM remodeling induced by human VLDL is\nstill unclear, as well as the influence of VLDL on the propensity to develop atherosclerosis.\nThe results obtained in this thesis indicate significant modifications in the production of\nthe major vascular proteoglycans in human endothelial cells depending on the endothelial\nphenotype in the setting of physiological levels of human VLDL. Together with this result,\nwe showed structural modifications in the chondroitin and dermatan sulfate (CS/DS)\nchains and changes in the expression of the main enzymes that regulate the chemical\ncharacteristics of the CS/DS chains, after VLDL treatment, in an atheroprotective\nendothelium. The thesis shows that VLDL could modulate the remodeling of matrix\nproteoglycans through the VLDL-receptor. This work emphasizes the potential application\nof therapies based on endothelial extracellular matrix remodeling to prevent\natherogenesis. |
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