DECREASE IN HIGH-DENSITY-LIPOPROTEIN BINDING-SITES IS ASSOCIATED WITHDECREASE IN INTRACELLULAR CHOLESTEROL EFFLUX IN DEDIFFERENTIATED AORTIC SMOOTH-MUSCLE CELLS

One of the key features of atherosclerosis formation and progression i s 'dedifferentiation' of contractile arterial smooth muscle cells (SMC ) in synthetic cells. In primary cultures and subcultures before 10 an d after 200 passages, SMC exhibit contractile-like, synthetic and tran sformed phenotypes, respectively, providing a good model for studing d edifferentiation process in vitro: the rationale for comparing these p henotypes 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 wa s to determine wether cholesterol metabolism undergoes changes in dedi fferentiated 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 apo protein mediated efflux and translocation but also with decrease in hi gh affinity binding sites for native HDL. Thus, the dedifferentiation process triggers a need for increased supply of cholesterol for membra ne synthesis and efflux down-regulation mechanisms are aimed at maximi zing cholesterol availability to the cell. Plasma membrane cholesterol efflux, which seems to be apoprotein-independent, decrease slightly w ith cell dedifferentiation suggesting either modifications in the dedi fferentiated cell membranes physical properties. Taken together, these different results showed that dedifferentiation of arterial SMC is as sociated with decrease in the different steps of the efflux process, w hich could constitute one of the early events in their foam cell trans formation.