Inducibleendothelin mRNA expression and peptide secretion in cultured human vascular smooth muscle cells

Thérèse J. Resink, Alfred W A Hahn, Timothy Scott-Burden, Jerry S Powell, Erika Weber, Fritz R. Bühler

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Abstract

This study demonstrates the induction of endothelin (ET) mRNA expression and synthesis of functional ET -peptide in cultured human vascular smooth muscle cells (hVSMC). Compounds eliciting such responses in hVSMC include the vasoconstrictor hormones angiotensin II and arginine-vasopressin and the growth factors transforming growth factor ß, platelet derived growth factor AA and epidermal growth factor. Induction of ET mRNA expression in hVSMC exhibited transient kinetics (peak at 3-5 hrs. and return to basal within 7 hrs.) which differed from the more sustained ET transcript induction observed for porcine endothelial cells. ET peptide (determined by both radioimmuno-and radioreceptor assays) produced by stimulated hVSMC attained levels (∼ 120-160 pg/106 cells/4 hrs.; concentration ∼ 3 × 10-11 M) within the biologically effective concentration range of ET. Stimulated secretion of ET from hVSMC was abolished in the presence of the protein synthesis inhibitor cycloheximide. Sep-pak C18 extracts of medium from stimulated hVSMC elicited a concentration-dependent phosphoinositide catabolic response in myo-[2-3H]-inositol-prelabelled hVSMC. Our findings invoke a role for ET which extends beyond the paracrine regulation by peptide synthesized and secreted by endothelial cells. We propose that VSMC-synthesized ET may function in an autocrine manner to regulate both tone and structural modelling of vasculature.

Original languageEnglish (US)
Pages (from-to)1303-1310
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume168
Issue number3
DOIs
StatePublished - May 16 1990
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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