Basic Fibroblast Growth Factor in Vascular Development and Atherogenesis

Abstract

Numerous laboratories are currently investigating the potential roles of polypeptide growth factors and oncogenes in atherosclerosis and related pathologies, such as restenosis after angioplasty and intimal proliferation in vessels of transplanted organs. Clearly, the rationale is that the development of these lesions involves the migration and proliferation of smooth muscle cells and monocyte-macrophages, and secretion of large amounts of extracellular proteoglycans and collagens (Ross et al. 1990a; Gerrity 1981; Gown et al. 1986; Wight 1989; Libby and Hansson 1991; Clowes and Schwartz 1985; McBride et al. 1988; Clowes et al. 1983; Manderson et al. 1989; Bulkley and Huchins 1977; Waller et al. 1984; Billingham 1989), well-known actions of growth factors, at least in vitro (Ross et al. 1990a; Gospodarowicz 1989; Baird and Böhlen 1990; Sporn and Roberts 1990). It is clear that most of the major classes of growth factors can by synthesized by activated macrophages (Ross et al. 1990a; Libby and Hansson 1991) and endothelial cells (Vlodavsky et al. 1987; Hannan et al. 1988; Speir et al. 1991; Baird and Ling 1987; Mansson et al. 1990; Gajdusek et al. 1980; Collins et al. 1987), and an increasing number of growth factors are being identified in vascular smooth muscle cells (Ross et al. 1990a; Libby and Hansson 1991; Baird and Ling 1987; Mansson et al. 1990; Weich et al. 1990; Gospodarowicz et al. 1988; Winkles et al. 1987; Cercek et al. 1990; Naftilan et al. 1989). Platelets have long been known to contain platelet-derived growth factors (PDGFs) (Ross et al. 1990a) and transforming growth factor-β (Sporn and Roberts 1990; Casscells et al. 1990a), and other mitogens such as serotonin (Corson et al. 1991).