Role of ABCA1 in HDL Formation andAtherosclerosis: Studies in ABCA1-Deficient Mice

摘要

I'd like to thank the organizers for giving me the opportunity to present some of our recent data on the consequences of ABCA1 (Figure 1) deletion on HDL levels, foam cell accumulation, and atherosclerosis in mice.What's important for my talk is that ABCAl-mediated cholesterol and phospholipid efflux is regulated by intercellular levels of sterols, and, as you heard many times, analogs of cAMP, and that ABCA1 is expressed in a number of tissues, including macrophages. At the time that the link between ABCA1 and Tangiers Disease was made, our transgenic group at Pfizer had already generated ABCA1 knockout mice. This was done in collaboration with our immunology group and Giovanni Camini. Omar Francone then characterized these mice, and he demonstrated that in these ABCA1 homozvgous animals there is a near complete absence of HDL, similar to what you see in the Tangiers patients.