Abstract. Different fibronectin (FN) variants arise from the single gene transcript alternatively spliced in a tissue-specific manner (Hynes, R. O. 1985. Annu. Rev. Cell Biol. 1:67-90; Owens, R. J., A. R. Kornblihtt, and E E. Baralle. 1986. Oxfi Surv. Eurcaryotic Genes. 3:141-160). We used mAb IST-9, specific for extra domain A (ED-A) FN sequence, and cDNA probe to ED-A exon to determine whether ED-A is present in FN synthesized by vascular smooth muscle cells (SMCs) and, if so, whether expression of ED-A is SMC phenotype dependent. ED-A-containing FN (A-FN) was not revealed in tunica media of human arteries and normal rat aorta by immunofluorescence and immunoblotting techniques. A eDNA probe to ED-A exon did not hybridize with RNA isolated from human aortic media. A positive reaction with IST-9 was observed in (a) diffuse intimal thickening and atherosclerotic plaque from human arteries; (b) experimentally induced intimal thickening in rat aorta; and (c) cultured vascular SMCs. A-FN mRNA was present in the RNA preparation from human aortic intima as judged by hybridization with eDNA probe to ED-A.On the other hand, an mAb interacting with an epitope common for all FN variants revealed FN in both intima and media of human arteries and in the normal rat aorta. A eDNA probe to a sequence shared by all FN variants hybridized with RNA from both intima and media of human aorta, though the level of expression was higher in intima. The data suggest that ED-A exon is omitted during splicing of the FN mRNA precursor in medial SMCs while the expression of A-FN is characteristic of "modulated" SMCs-those of intimal thickenings, of atherosclerotic lesions, and growing in culture.F IBRONECTINS (FNs) ~ are high molecular weight glycopmteins playing an important role in different cellular phenomena-e.g., adhesion, migration, and differentiation-and, thereby, in embryogenesis, wound healing, hemostasis, and thrombosis (26,35,61). The FN molecule is a dimer with a subunit mass of ,x,250,000 D. The primary structure of FN has been studied both on protein (human and bovine FN) and cDNA (chicken, rat, and human FN) levels (7, 16-18, 32, 38, 42, 45, 50, 53, 55). The FN subunit is composed of three different kinds of repeating sequences (32,45,53). Two fibrin-binding domains, NH2 and COOH terminal, and a collagen-binding domain, NH2 terminal, are made up of 45-5G--amino acid-long repeats types I and II, while a 90-amino acid-long repeat type HI composes the central 150,000-180,000-D part of the FN subunit (45, 53). Subtle alterations in subunits give rise to various FN forms. Cir- Abbreviations used in this paper:A-FN, fibronectin containing extra domain A sequence; cFN, cellular fibronectin; ED-A, extra domain A; ED-A-FN, fibronectin that lacks ED-A; FN, fibronectin; pFN, plasma fibronectin; SM, smooth muscle; SMC, smooth muscle cell. culating form, or plasma FN (pFN), is synthesized by hepatocytes; fibroblasts, endothelial cells, and some other cells produce cellular FN (cFN), which is accumulated in the insoluble extracellular ...

A heparin-binding protein was isolated from bovine uteri and purified to homogeneity. This protein appears as a double band of approx. 78 kDa in SDS/polyacrylamide-gel electrophoresis and has an isoelectric point of 5.2. The binding of heparin to this protein is saturable. No other glycosaminoglycan from mammalian tissue, such as hyaluronic acid, chondroitin sulphate, dermatan sulphate or keratan sulphate, binds to the 78 kDa protein. Dextran sulphate binds in a non-saturable fashion. Certain heparan sulphate polysaccharide structures are required for binding to the 78 kDa protein. Some proteoheparan sulphates, such as endothelial cell-surface proteoheparan sulphate, show only weak interaction with the 78 kDa protein in contrast with a basement-membrane proteoheparan sulphate from HR-9 cells. Antibodies against the 78 kDa protein inhibit binding of proteoheparan [35S]sulphate from basement membranes to smooth-muscle cells. Conventional antibodies, Fab fragments and some monoclonal antibodies, inhibit smooth-muscle cell proliferation in a similar range as that observed for heparin. The protein was detected in a variety of tissues and cells but not in blood cells. A possible role of this protein as a receptor for heparin or heparan sulphate and its function in the control of the arterial wall structure are discussed.

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Daily consumption of food products enriched with carob fibre shows beneficial effects on human blood lipid profile and may be effective in prevention and treatment of hypercholesterolemia.