Vascular smooth muscle growth: Autocrine growth mechanisms

Vascular smooth muscle cells (VSMC) exhibit several growth responses to ago nists that regulate their function including proliferation (hyperplasia wit h an increase in cell number), hypertrophy (an increase in cell size withou t change in DNA content), endoreduplication (an increase in DNA content and usually size), and apoptosis. Both autocrine growth mechanisms (in which t he individual cell synthesizes and/or secretes a substance that stimulates that same cell type to undergo a growth response) and paracrine growth mech anisms (in which the individual cells responding to the growth factor synth esize and/or secrete a substance that stimulates neighboring cells of anoth er cell type) are important in VSMC growth. In this review I discuss the au tocrine and paracrine growth factors important for VSMC growth in culture a nd in vessels. Four mechanisms by which individual agonists signal are desc ribed: direct effects of agonists on their receptors, transactivation of ty rosine kinase-coupled receptors, generation of reactive oxygen species, and induction/secretion of other growth and survival factors. Additional growt h effects mediated by changes in cell matrix are discussed. The temporal an d spatial coordination of these events are shown to modulate the environmen t in which other growth factors initiate cell cycle events. Finally, the he terogeneous nature of VSMC developmental origin provides another level of c omplexity in VSMC growth mechanisms.