Fabp4 i biomarcadors de la disfunció endotelial. Estudi clínic i in vitro

The coexistence of multiple cardiovascular risk factors such as metabolic syndrome, abdominal obesity, dyslipidemia and insulin resistance, determine the onset of endothelial dysfunction, the first event in the pathogenesis of atherosclerosis. The peripheral arterial tonometry (PAT) is a novel and n...

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Detalhes bibliográficos
Autor: Aragonés Bargalló, Gemma
Formato: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2010
País:España
Recursos:Universitat Rovira i virgili (URV)
Repositorio:Repositori Institucional de la Universitat Rovira i Virgili
OAI Identifier:oai:urv.cat:TDX:663
Acesso em linha:https://hdl.handle.net/20.500.11797/TDX663
http://hdl.handle.net/10803/8885
Access Level:acceso abierto
Palavra-chave:616.1 - Patologia del sistema circulatori, dels vasos sanguinis. Trastorns cardiovasculars
61 - Medicina
577 - Bioquímica. Biologia molecular. Biofísica
Descrição
Resumo:The coexistence of multiple cardiovascular risk factors such as metabolic syndrome, abdominal obesity, dyslipidemia and insulin resistance, determine the onset of endothelial dysfunction, the first event in the pathogenesis of atherosclerosis. The peripheral arterial tonometry (PAT) is a novel and noninvasive technique which allows the assessment of endothelial function at the clinical level. Moreover, recent scientific evidence suggests that FABP4 circulating, adipokyne secreted by adipose tissue, could have a direct effect on peripheral tissues. Therefore, high levels of FABP4 might be involved in arterial damage and endothelial dysfunction. To perform the clinical assessment were recruited patients with moderate cardiovascular risk (CV). The endotehlial function was assessed by PAT. Antropometry, circulating endothelial, lipid oxidation and inflammation biomarkers and FABP4 were measured. In vitro, was working in endothelial cells HUVECs and leukocyte (Jurkat T cells), and were quantified protein expression and mRNA. The results were clinically significant in that the sE-selectin (endothelial adhesion molecule) and oxidized LDL are associated inversely with RHI-PAT in patients with moderate CV risk. The plasma FABP4 was inversely associated with RHI-PAT in patients with type 2 diabetes. In vitro, FABP4 might modulate insulin signaling, decreasing the phosphorylations pathways (Akt and eNOS) and increasing the expression of adhesion molecules (VCAM1 and E-selectin), inducing endothelial dysfunction and insulin resistance in endothelial cells. We conclude that sE-selectin and oxidized LDL are associated with RHI-PAT in patients with CV risk by supporting the role of PAT in the clinical assessment of endothelial function and circulating FABP4 levels are associated with