Estudo da relação entre a expressão da proteina de transferencia de colesteril ester, diabetes e aterosclerose em camundongos transgenicos

AUTOR(ES)

Jairo Augusto Berti

DATA DE PUBLICAÇÃO

2003

RESUMO

Cholesteryl ester transfer protein (CETP) mediates cholesteryl ester and triglyceride redistribution among plasma lipoproteins. Contrasting effects of variations in CETP expression and presence of diabetes on the extension of atherosclerosis have been reported in distinct animal models and metabolic contexts. The CETP expression was studied in streptozotocin induced diabetic, in glucose fed, in glucose fed plus hyperinsulinemic and in control transgenic mice. The results showed that: 1- insulin deficiency and hyperglycemia increase CETP plasma levels and liver mRNA expression; 2- glucose supplementation increases CETP expression by post-transcriptional mechanisms; and 3- hyperinsulinemia downregulates the glucose-stimulated CETP expression by reducing its mRNA levels. In a second study, the effects of diabetes and CETP expression on the diet induced atherosclerosis in LDL receptor deficent mice were evaluated. The results showed that: 1CETP expression does not alter the responsiveness of lesion formation to diabetes, although it may be protective in euglycemic state, 2- triglyceride concentration is an independent risk factor in LDL receptor deficient mice but not in CETP expressing mice, 3- plasma cholesterollevels significantly increase the chances of developing large size atherosclerotic lesions, independently of genotype and presence of diabetes, and 4hyperglycemia contributes to the risk of atherosclerosis. In a third study, we investigated the effects of over-expressing three genes involved in the reverse cholesterol transport: apolipoprotein AI, lecithin-cholesterol acyl transferase (LCA T) and CETP on the development of diet induced atherosclerosis in aged mice. The results showed that: 1- LCA T and LCA T / AI expression impose a higher risk of developing atherosclerosis, 2- CETP expression on these backgrounds neutralizes this atherogenic scenario, and 3- isolated, apoAI overexpression reduces the chances of developing large size atherosclerotic lesions

ASSUNTO(S)

insulina lipoproteinas aterosclerose

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