TISSUE & CELL 1987 19 (1) l-19 0 1987 Longman Group UK Ltd zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGF IRA M. HERMAN EXTRACELLULAR MATRIX-CYTOSKELETAL INTERACTIONS IN VASCULAR CELLS Keywords: Actin, angiogenesis, atherosclerosis, blood vessels, contractile proteins, cyto- skeleton, extracellular matrix, injury zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML Introduction Recent work in the fields of vascular phy- siology and cell biology has refined our understanding of the fundamental prop- erties of the major cells residing in the blood vessel wall. The interactions of the vascular endothelium with the formed ele- ments of the blood, basal lamina and med- ial smooth muscle cells (SMC) have been and continue to be intensively studied. Model systems have been established with the aim of examining and characterizing the specific processes that regulate vascular cell behavior during development, differentia- tion, and in association with the disease state. In this review I will consider some of the recent work focused on the role that the extracellular matrix (ECM) plays in signal- ling the cytoskeleton of vascular cells. Ulti- mately, these data will be organized into a working model that may explain some of the early events in the atherogenetic path- way. It is neither my intention nor my goal to include the vast literature reviewing other critical aspects of blood vessel struc- ture and function; for this information, Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111. Received 1 September 1986. 1 cogent reviews can be found (Auerbach, 1981; Bjorkerud, 1979; Brown and Gold- stein, 1984; Folkman, 1983; Gimbrone, 1981; Glagov, 1984; Goldstein and Brown, 1977; Leary 1941; McGill, 1968, 1984; Mitchell and Schwartz, 1965; Ross, 1986; Ross and Glomset, 1976; Schwartz zyxwvutsrqponmlk et al., 1982, 1985). A. The Microvasculature 1. Microvessels zyxwvutsrqponmlkjihgfedcbaZYX in viva It is clear that the development of the blood vascular system proceeds through an intri- cate series of steps that include the migra- tion, proliferation and adhesion of the vascular cells. Current thinking in the field indicates that the ECM modifies endothelial cell (EC) behavior (Clark and Clark, 1925, 1939; Krogh, 1929; Alessandri et al., 1983; Auerbach et al., 1976; Ausprunk and Folk- man, 1977; Gospodarowicz et al., 1980; Greenburg and Gospodarowicz, 1982) dur- ing normal development, wound healing or in association with a number of pathological processes that include tumor angiogenesis and diabetic retinopathy (Folkman, 1974, 1975; Ben-Ezra, 1979; Rifkin et al., 1983; 1984; Wise, 1956). In growing capillaries the advancing tip consists of elongate EC that synthesize and secrete complex unsul- fated carbohydrates. Hyaluronic acid pre-