"Effetti cellulari e molecolari del difetto di ABCA1 nella malattia di Tangier"

HDLs (High Density Lipoproteins) are the smallest and densest of the plasma lipoproteins. One of the most severe forms of familial HDL deficiency is Tangier disease (TD), a genetic disorder characterized by extremely low levels of HDL and Apolipoprotein A-I and by the cholesteryl esters accumulation in many tissues. This disorder is often associated with an increased risk of coronary artery disease (CAD). The clinical phenotype of Tangier disease is inherited as an autosomal recessive trait, and the biochemical phenotype is inherited as an autosomal codominant trait. Tangier disease is caused by mutations in the gene of the ATP-binding cassette transporter 1 (ABCA1), which encodes the membrane transporter ABCA1. Thesis‘ aim regards the study of skin fibroblast of the TD1 patient, heterozygote for ABCA1 mutation, and the TD2 patient, homozygous. Cells from various types of aging syndromes and cardiovascular diseases, have an in vitro reduced proliferative capacity and exhibited cellular senescence at the earlier passage. We investigated whether TD and FHD fibroblasts exhibit cellular senescence at the earlier passage than controls. We also used FHD and TD fibroblasts to study the difference in gene expression of some molecules that play a key role in the cholesterol efflux: ABCG1 and LDLr