title: Decreased susceptibility of cultured smooth muscle cells from SHR rats to growth inhibition by heparin.
abstract: Smooth muscle cell proliferation is regulated through the coordinated action of growth inhibitors and growth factors/mitogens; a specific heparin-epidermal growth factor (EGF) complementation has been proposed (Reilly et al., 1987, J. Cell. Physiol., 131:149-157). In culture, vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) proliferate more rapidly than VSMC from control Wistar Kyoto rats (WKY). We observed that, compared with WKY-derived VSMC, cells from SHR were markedly less susceptible to growth inhibition both by heparin and its homopolysaccharide analogue pentosan polysulphate (PPS). SHR-derived VSMC exhibited a reduced capacity for binding of [3H]heparin to specific extracellular surface receptors, whereas affinities for heparin were comparable between both VSMC isolates. The early (0-2 hr at 37 degrees C) kinetics of internalization did not differ between SHR- and WKY-derived VSMC, but both internalized equivalent proportions (approximately 10%) of initially surface-bound heparin. VSMC from SHR exhibited a greater capacity, without a changed affinity, for [I125]EGF binding than VSMC from WKY. Pre-exposure of VSMC to heparin or PPS decreased, in a time-dependent manner, the EGF binding capacity for both SHR and WKY (by 40-50% after 72 hr). However, in absolute terms, the EGF-binding capacity of VSMC from SHR exposed to heparinoids was similar to that of nonexposed VSMC from WKY.
authors.affiliation: Department of Research, University Hospital, Basel, Switzerland.
authors.forename: T J
authors.initials: TJ
authors.lastname: Resink
authors.forename: T
authors.initials: T
authors.lastname: Scott-Burden
authors.forename: U
authors.initials: U
authors.lastname: Baur
authors.forename: M
authors.initials: M
authors.lastname: Bürgin
authors.forename: F R
authors.initials: FR
authors.lastname: Bühler
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D006493:Heparin