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Induction of vascular smooth muscle cell growth by selective activation of the thrombin receptor Effect of heparin
Author(s) -
Herbert J.M.,
Lamarche I.,
Dol F.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81237-g
Subject(s) - thrombin , agonist , peptide , receptor , chemistry , thrombin receptor , heparin , biochemistry , cell growth , vascular smooth muscle , biology , endocrinology , platelet , smooth muscle , immunology
The synthetic peptide, SFLLRNPNDKYEPF, has been recently described as a peptide mimicking the new amino‐terminus created by cleavage of the thrombin receptor, therefore acting as an agonist of the thrombin receptor. This peptide was a potent mitogen for rabbit arterial smooth muscle cells (SMC) and exhibited the same activity as that of native α‐thrombin. Both compounds stimulated the proliferation of growth‐arrested SMCs with half‐maximum mitogenic responses at 1 nM. NAPAP, a synthetic inhibitor of the enzymatic activity of thrombin, specifically inhibited thrombin‐induced SMC growth (IC 50 = 0.35 ± 0.04 μM) but was without effect on the mitogenic effect of the agonist peptide. These results therefore demonstrate that the mitogenic effect of α‐thrombin for SMCs is intimately linked to its esterolytic activity. Heparin, which inhibited fetal calf serum‐induced SMC growth, was without effect on thrombin‐induced SMC growth but strongly reduced the mitogenic effect of the agonist peptide (IC 50 = 32 ± 5μ/ml). This effect was not related to the anti‐coagulant activity of heparin but was highly dependent on molecular mass and on the global charge of the molecule and was also observed for other sulphated polysaccharides such as pentosan polysulphate.