Ativação da via nNOS/H2O2 pela atorvastatina: implicações na disfunção endotelial induzida por lisofosfatidilcolina

• Ano de defesa: 2015
• Autor(a) principal: Gianne Paul Campos Mota
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Fisiologia e Farmacologia; Farmacologia; Fisiologia
• Link de acesso: http://hdl.handle.net/1843/BUBD-A3YGCU

Atherosclerosis is a chronic disease related to an inflammatory response caused by the increase of Lysophosphatidylcholine (LPC) - a component of oxidized LDL (oxLDL) - that is the key factor for the inflammatory response, endothelial dysfunction development and progression of atherosclerotic plaque. Nitric oxide synthases (NOS) present a well-established role in the maintenance of vascular homeostasis. NOS deficiency is commonly related to endothelial dysfunction that precedes plaque deposition. However, the contribution of neuronal NOS (nNOS) on endothelial dysfunction induced by dyslipidemia is not known. Moreover, the mechanisms involved in the modulation of nNOS expression and activity by oxLDL on endothelial cells are completely unknown. On the other hand, some works suggested that statins (HMG-CoA reductase inhibitors; inhibitors of endogenous cholesterol synthesis) present direct beneficial effects on cardiovascular system, independently of cholesterol reduction. Some statins could activate or increase the expression of NOS, specially nNOS. By these reasons, we aimed to evaluate the role of nNOS on endothelial dysfunction induced by LPC and its role on the protection mediated by atorvastatin in a model of organ bath and in cultures of immortalized human endothelial cells. Were evaluated NOS in experiments by vascular reactivity. NO and H2O2 production by endothelial cells were measured by flow citometry. The contribution of nNOS was evaluated by the pharmacological nNOS inhibition by TRIM. Our results suggested by the first time that acute treatment with LPC was able to induce endothelial dysfunction that was prevented by the use of atorvastatin by NOS stimuli. These findings were confirmed by flow citometry, that demonstrated an increase of NO and H2O2, by the treatment with atorvastatin and a reduction with LPC. Finally, we showed that atorvastatin presented a protective effect on endothelial cells by upregulate nNOS activity and, consequently, preventing endothelial dysfunction mediated by LPC.