title: Heparin and the phenotype of adult human vascular smooth muscle cells.
abstract: To study mechanisms controlling growth and phenotype in human vascular smooth muscle cells, we established culture conditions under which these cells proliferate rapidly and achieve life-spans of 50-60 population doublings. In medium containing heparin and heparin-binding growth factors, growth rate and life-span of human vascular smooth muscle cells increased more than 50% relative to cultures with neither supplement, and more than 20% compared to cultures supplemented only with heparin-binding growth factors. In contrast to observations made in rat vascular smooth muscle cells, smooth muscle-specific alpha-actin in the human cells was expressed only in the presence of heparin and colocalized with beta/gamma nonmuscle actins in stress fibers, not in adhesion plaques. Heparin, in the presence of heparin-binding growth factors, also caused more than 170% stimulation of tracer glucosamine incorporation into hyaluronic acid and a 7.5-fold increase in hyaluronic acid accumulation. In comparison, total sulfate incorporation into sulfated glycosaminoglycans increased by less than 40%. In light of our previous findings that heparin suppresses collagen gene expression, we conclude that heparin induces human vascular smooth muscle cells exposed to heparin-binding growth factors to remodel their extracellular matrix by altering the relative rates of hyaluronic acid (HA) and collagen synthesis. The resulting hyaluronic-acid-rich, collagen-poor matrix may enhance infiltration of CD44/hyaluronate-receptor-bearing T-lymphocytes and monocytes into the vascular wall, an early event in atherogenesis.
authors.affiliation: Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sorger
authors.forename: N
authors.initials: N
authors.lastname: Friday
authors.forename: L D
authors.initials: LD
authors.lastname: Yang
authors.forename: E M
authors.initials: EM
authors.lastname: Levine
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000328:Adult; D000818:Animals; D001483:Base Sequence; D018929:Cell Culture Techniques; D002455:Cell Division; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D015345:Oligonucleotide Probes; D010641:Phenotype; D051381:Rats
chemical_list: D000199:Actins; D006025:Glycosaminoglycans; D006133:Growth Substances; D015345:Oligonucleotide Probes; D006820:Hyaluronic Acid; D006493:Heparin