EXPRESSION OF CAVEOLAE ON THE SURFACE OF RAT ARTERIAL SMOOTH-MUSCLE CELLS IS DEPENDENT ON THE PHENOTYPIC STATE OF THE CELLS

Both after vascular injury and when established in vitro, arterial smo oth muscle cells pass through a characteristic change in phenotype. Th is process includes a prominent structural reorganization with partial loss of myofilaments and formation of a large endoplasmic reticulum a nd Golgi complex. As a result, the cells lose their contractility and become able instead to divide and to secrete extracellular matrix comp onents. In the present study, the expression of plasma membrane caveol ae in rat arterial smooth muscle cells was studied in primary culture and during the formation of neointimal thickenings after balloon injur y. Electron microscopic analysis revealed that the number of caveolae (identified as flask-shaped invaginations of the plasma membrane) was reduced when the cells converted from a contractile to a synthetic phe notype (as defined morphologically) and then increased again when they readopted a more differentiated state. However, immunoblotting analys is did not show any changes in the cellular content of caveolin (a maj or protein component of caveolae) during the Ist week in culture. At t he same time, immunocytochemical staining demonstrated a shift in the localization of caveolin from small spot-like structures dispersed ove r the cell surface to vesicular structures in the perinuclear cytoplas m. These findings indicate that the transition of smooth muscle cells from a contractile to a synthetic phenotype involves a marked decline in the number of plasma membrane caveolae. In parallel, caveolin is in ternalized and redistributed to Golgi-associated vesicles in the perin uclear cytoplasm. In context of the rapidly increasing awareness of th e importance of caveolae both in signal transduction and intracellular cholesterol transport, it seems likely that the Variations in the num ber of caveolae may be significant for the functional differences betw een smooth muscle cells in different phenotypes.