Decrease in high density lipoprotein binding sites is associated with decrease in intracellular cholesterol efflux in dedifferentiated aortic smooth muscle cells

Abstract

One of the key features of atherosclerosis formation and progression is ‘dedifferentiation’ of contractile arterial smooth muscle cells (SMC) in synthetic cells. In primary cultures and subcultures before 10 and after 200 passages, SMC exhibit contractile-like, synthetic and transformed phenotypes, respectively, providing a good model for studing dedifferentiation process in vitro: the rationale for comparing these phenotypes to SMC in vivo rests in similar changes in cytoenzymatic and cytoskeletal features. In vivo, dedifferentiated SMC are transformed into foam cells by accumulating lipids. Thus, the aim of this study was to determine wether cholesterol metabolism undergoes changes in dedifferentiated cells and the three cultured phenotypes were compared in regard to their cholesterol efflux mechanisms. Phenotypic changes were shown to be associated with decrease in intracellular cholesterol apoprotein mediated efflux and translocation but also with decrease in high affinity binding sites for native HDL. Thus, the dedifferentiation process triggers a need for increased supply of cholesterol for membrane synthesis and efflux down-regulation mechanisms are aimed at maximizing cholesterol availability to the cell. Plasma membrane cholesterol efflux, which seems to be apoprotein-independent, decrease slightly with cell dedifferentiation suggesting either modifications in the dedifferentiated cell membranes physical properties. Taken together, these different results showed that dedifferentiation of arterial SMC is associated with decrease in the different steps of the efflux process, which could constitute one of the early events in their foam cell transformation.