title: A paradoxical pro-apoptotic effect of thrombin on smooth muscle cells.
abstract: Whereas thrombin (below 10 nM) is a potent mitogen, recent studies report that exposure to higher doses of thrombin could lead to apoptosis of neurons and tumor cells. Our results show that prolonged exposure (> or = 24 h) to thrombin (50-100 nM) exerts a pro-apoptotic effect on cultured vascular smooth muscle cells (VSMCs). This phenomenon depends on thrombin serine-protease activity but is independent of PAR-1 and -4 activation and subsequent signaling. The parallel occurrence of cell retraction and cleavage of fibronectin suggests that thrombin-induced apoptosis is consecutive to pericellular proteolysis. These data point to a new potential action of thrombin in the cardiovascular system.
authors.affiliation: INSERM U460, CHU X. Bichat, 75877, Paris, Cedex 18, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Bouton
authors.forename: Martine
authors.initials: M
authors.lastname: Jandrot-Perrus
authors.forename: Marijke
authors.initials: M
authors.lastname: Bryckaert
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Jacob
authors.forename: Annie
authors.initials: A
authors.lastname: Bezeaud
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guillin
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005109:Extracellular Matrix; D005353:Fibronectins / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D044463:Receptor, PAR-1 / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D044463:Receptor, PAR-1; D016212:Transforming Growth Factor beta; C101296:prostate apoptosis response-4 protein; D013917:Thrombin; D020778:Matrix Metalloproteinase 2; D002118:Calcium