16] CONVENTIONAL RISK FACTORS AND PROGNOSTIC LOCALIZATION OF CORONARY ARTERY DISEASE (original) (raw)

performed in order to detect ABCA1 protein. Cholesterol efflux to lipid free ApoA-I was measured in FH and control fibroblasts treated with 22OH/cRA. Results: Western Blot analysis showed that the basal expression of ABCA1 was markedly reduced in all FH cells compared to wild type cells. Stimulation of ABCA1 expression upon cholesterol loading resulted in the upregulation of ABCA1 protein both in wild type and FH fibroblasts, but the extent of the upregulation was highly variable among different FH cells and was always below that obtained in control cells. In addition the direct stimulation of ABCA1 gene transcription, obtained by treatment of cells with 22OH-cholesterol and 9cis-Retinoic Acid (22OH/cRA), did not restore ABCA1 expression level in FH cells to that exhibited by control cells. Cholesterol efflux to lipid free ApoA-I was measured in FH and control fibroblasts upon treatment with 22OH/cRA. As expected, all FH cells showed a reduced ABCA1dependant efflux with respect to control cells. Conclusions: These results suggest that an impairment in ABCA1 expression and function might be responsible for low plasma HDL-C levels of FH patients. The observation that LXR agonists failed to restore full ABCA1 expression, suggest the involvement of other regulatory mechanisms, such as permanent activation of SREBP transcription which could hamper LXR activation, as observed in LDLR / murine macrophages.