Efeito antiinflamatorio da S-nitroso-N-acetilcisteina (SNAC) na aterogenese em camundongos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

Background: Several inflammatory pathways have been shown to participate in the atherosclerotic process. Different markers for inflammation and endothelial dysfunction have been found to predict the future risk for developing cardiovascular disease. Newer markers such as CD40 ligand appear to provide important information regarding clinical risk. In hypercholesterolemic LDLr-/- mice, we addressed anti-inflammatory effects of the nitrosothiol ?NO donor S-nitroso-N-acetylcysteine (SNAC) in the early prevention of plaque development as well as changes in blood pressure and ?NO synthase expression. Methods and Results: LDLr-/- mice fed with 0.5 % colic acid and 1.25 % cholesterol-enriched diet showed increased aortic expression of CD40L that was related to initial (HC 15d) and advanced (HC 60d) phases and inversely related with ?-actin expression. Expression of eNOS and nNOS was higher in the LDLr-/- than Wild Type (C57BL6) mice, as well as, there was a larger expression of three isoforms of NOS in LDLr-/- mice fed with HC diet. Increase in the blood pressure was present in LDLr-/- in relation to Wild Type mice. SNAC administration (0.51 mmol/Kg/day i.p. for 15 days) promoted 49% of reduction in atherosclerotic lesion area associated with the prevention of this increased NOS and CD40L expression but without alterations in the increased blood pressure. Conclusion: We concluded that the genetic deletion of LDL receptor in mice produced alterations on the markers proposed to the inflammation and endothelial dysfunction, and showed to be responsible for hypertension, both characterized in this animal model. The SNAC treatment showed efficacy in the prevention of atheroma establishment by anti-inflammatory process. Nevertheless, the SNAC treatment was not capable to promote alterations in the increased blood pressure, which was verified in these ko mice

ASSUNTO(S)

mice nitric oxide inflammation astherosclerosis lipoproteinas oxido nitrico inflamação camundongo aterosclerose lipoproteins

ACESSO AO ARTIGO

Documentos Relacionados