The expression and function of G-proteins in experimental intimal hyperplasia

Mark G. Davies, Vickram Ramkumar, Tom W. Gettys, Per Otto Hagen

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

G-proteins are membrane-bound signal transduction proteins which couple extracellular receptor signals to various effectors. This study examines the expression and the function of G-proteins (α(i), α(s), α(q), and α(o)) in experimental intimal hyperplasia. Vein bypass grafts were placed in 30 New Zealand White rabbits and were harvested after 28 d. The contralateral jugular veins served as controls. Isometric tension studies were performed on rings from veins and vein grafts (n = 10), and Western blot and mRNA analyses were performed in another 20 vessels. There was a fivefold increase in α(q), a 2.7-fold increase in the α(i2), and a 3.3-fold increase in α(s) expressions in vein grafts compared with veins. Detectable expression of α(i3) was observed in vein grafts but not in jugular veins. In addition, there was a 3.8-fold increase in β subunits in the vein grafts compared with the veins. mRNA for α(s), α(i3), and α(i2) were all elevated in the vein grafts. No detectable levels of the α(i1) protein or its mRNA were present in either veins or vein grafts. Contractile responses in the veins were not inhibited by pertussis toxin. The contractile responses to norepinephrine were enhanced by twofold, and the responses to serotonin developed de novo in vein grafts compared with veins. The contractile responses to both norepinephrine and serotonin were only partially inhibited by pertussis toxin in the vein grafts even though there was 100% ADP ribosylation with pertussis toxin in both veins and vein grafts. These data suggest that intimal hyperplasia is associated with increased or novel expression of G-proteins in vivo which occur simultaneously with the development of pertussis toxin- sensitive contractile responses. Changes in G-proteins at a transcriptional level or at the level of RNA stability may be involved in the response of smooth muscle cells to injury and to intimal hyperplasia formation.

Original languageEnglish (US)
Pages (from-to)1680-1689
Number of pages10
JournalJournal of Clinical Investigation
Volume94
Issue number4
DOIs
StatePublished - Oct 1994

Keywords

  • G-proteins
  • intimal hyperplasia
  • rabbit
  • smooth muscle cells
  • vein graft

ASJC Scopus subject areas

  • Medicine(all)

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