ROLE OF CAVEOLAE IN CHOLESTEROL TRANSPORT IN ARTERIAL SMOOTH-MUSCLE CELLS EXPOSED TO LIPOPROTEINS IN-VITRO AND IN-VIVO

Arterial smooth muscle cells are able to shift between two major diffe rentiated states with distinct morphologic and functional properties, a contractile phenotype and a synthetic phenotype. Recently, it was de monstrated that contractile smooth muscle cells have numerous caveolae and that these specialized regions of the plasma membrane, to a large extent, are lost when the cells are modified into a synthetic phenoty pe. At the same time, the levels of the cholesterol-binding membrane p rotein caveolin remained unchanged and caveolin was redistributed from the cell surface to the perinuclear cytoplasm. In the present investi gation, electron microscopy was used to study how smooth muscle cells of different phenotypes react to exposure to low-density lipoprotein a nd other lipoproteins both in vitro and in vivo. Our findings indicate that contractile cells (present early in primary culture and in the m edia of normal arterial walls) do not accumulate lipids in the cytopla sm and release excess cholesterol by means of plasma membrane caveolae . Extracellularly, the expelled lipids were built into membranous conf igurations and piled up as myelin-like deposits. In synthetic cells (f ormed after a few days in primary culture and as a response to arteria l injury), lipids gathered in cytoplasmic droplets and increased amoun ts of membranous inclusions appeared in endosomes and lysosomes. On th e other hand, no signs of extracellular discharge of lipids were detec ted. The results suggest that contractile smooth muscle cells use cave olin and caveolae to free themselves of excess lipoprotein-derived cho lesterol and so manage to maintain a balance in the influx and efflux of cholesterol. Synthetic smooth muscle cells show a Golgi-like immuno staining for caveolin but have an insufficient capacity to use this pr otein to transport cholesterol to the plasma membrane and out of the c ell. Cholesterol will then rather be esterified and collect in lipid d roplets, eventually leading to foam cell formation if the uptake of li poprotein continues.