PMID: 9546238Apr 18, 1998Paper

Heparin inhibits thrombin-induced mitogen-activated protein kinase signaling in arterial smooth muscle cells

Journal of Vascular Surgery
U HedinA W Clowes

Abstract

Smooth muscle cell proliferation is a key event in the development of intimal hyperplasia after arterial injury. Heparin can suppress smooth muscle cell proliferation in vitro and prevents intimal hyperplasia after arterial injury, but the mechanisms of action are poorly understood. Recently, we observed that heparin inhibited serum-induced activation of mitogen-activated protein kinase in smooth muscle cells, but heparin did not inhibit signaling induced by platelet-derived growth factor BB and basic fibroblast growth factor, both ligands of tyrosine kinase receptors. Here, we examined the possibility that heparin inhibits signaling by thrombin and other activators of heterotrimeric G-proteins. Baboon aortic smooth muscle cells were stimulated with thrombin, angiotensin II, endothelin-1, and lysophosphatidic acid in the presence or absence of heparin. After stimulation, mitogen-activated protein kinase activity was measured with an in-gel phosphorylation assay, mitogen-activated protein kinase kinase-1 was immunoprecipitated from the same samples, and activity was measured with recombinant mitogen-activated protein kinase as a substrate. DNA synthesis was measured by 3H-thymidine labeling and scintillation counting. Heparin in...Continue Reading

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Citations

Mar 26, 2010·Tissue Engineering. Part B, Reviews·Jeffrey A BeamishRoger E Marchant
Sep 1, 2007·Journal of Cellular and Molecular Medicine·Ken A LindstedtPetri T Kovanen
May 22, 2002·Journal of Vascular Surgery·Jean-François DeuxDidier Letourneur
Dec 9, 2000·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·P ReligaU Hedin
Feb 22, 2002·The Journal of Surgical Research·J Jeffrey Alexander, Isabel Lewis
Sep 17, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Rekha C PatelChandrashekhar V Patel
Feb 26, 2005·The Journal of Biological Chemistry·Stephen FascianoChandrashekhar V Patel
Oct 18, 2002·Journal of Cellular Physiology·Monsur KaziUlf Hedin
Dec 11, 2013·Translational Stroke Research·Norihito Shimamura, Hiroki Ohkuma
Jan 25, 2002·Annals of the New York Academy of Sciences·A KalmesA W Clowes
May 6, 2004·Journal of Hypertension·Rodney J DilleyJohn F Bertram
Aug 28, 2009·Biomaterials·Jeffrey A BeamishRoger E Marchant
Dec 22, 1999·Biochemical and Biophysical Research Communications·T E PetersonR D Simari

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