Induction of vascular smooth muscle cell growth by selective activation of the proteinase activated receptor-2 (PAR-2)

Biochemical and Biophysical Research Communications
F BonoJ M Herbert

Abstract

The proteinase-activated receptor (PAR-2) which belongs to the family of proteolytically cleaved receptors is activated by trypsin and by a synthetic peptide (SLIGKV) derived from the new amino terminus. Here, we have studied the mitogenic effect of trypsin and of SLIGKV on human aortic smooth muscle cells (SMC). Like trypsin, SLIGKV was a potent mitogen for SMC and exhibited the same activity as that of SFLLRN, a peptide mimicking the new amino terminus created by cleavage of the thrombin receptor. SLIGKV stimulated the proliferation of growth-arrested SMCs with a half-maximum mitogenic response at 80 nM. Under the same experimental conditions, the retro analogue or SLIGKV (VKGILS) did not show any mitogenic activity. Two specific inhibitors of the enzymatic activity of trypsin, alpha 1-antitrypsin and aprotinin, specifically inhibited trypsin-induced SMC growth (IC50 = 0.87 +/- 0.09 and 0.74 +/- 0.11 microM, respectively) but remain without effect on the mitogenic effect of the agonist peptide. The mitogenic effect of trypsin and SLIGKV was due to the release of platelet derived growth factor as demonstrated by the inhibitory activity of a neutralizing monoclonal anti-PGDF-BB antibody. These results demonstrate that the mitog...Continue Reading

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Citations

Jan 12, 2002·British Journal of Pharmacology·Carla Cicala
Mar 30, 2004·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·Chris R TriggleMalarvannan Pannirselvam
Feb 14, 2012·Pharmacology & Therapeutics·Hannah Lee, Justin R Hamilton
Mar 26, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Rosealee SmithEleanor J Mackie
Jul 22, 2014·British Journal of Clinical Pharmacology·Antonio J López-FarréGuillermo Moñux
Feb 24, 2005·Journal of Atherosclerosis and Thrombosis·Kousuke MarutsukaYujiro Asada
Jul 13, 2001·Pulmonary Pharmacology & Therapeutics·T M Cocks, J D Moffatt
Jan 19, 2005·Journal of Pharmacological Sciences·Masahiro NishiboriHideo K Takahashi
Jun 1, 2018·Journal of Thrombosis and Haemostasis : JTH·B M M KremersH M H Spronk
Mar 31, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Shannon M JonesA Phillip Owens
Feb 5, 2010·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Hong LiuLin Sun
Apr 21, 2001·Journal of Neural Transmission·T OkamotoK Saeki
Jul 6, 2000·Developmental Dynamics : an Official Publication of the American Association of Anatomists·A L JenkinsE J Mackie
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Jul 23, 2003·Journal of the American Society of Nephrology : JASN·Giuseppe GrandalianoFrancesco P Schena
Feb 28, 2002·Journal of Hepatology·Marianna D A GaçaR Christopher Benyon

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