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A paradoxical pro-apoptotic effect of thrombin on smooth muscle cells
Patrick Rossignol1, Marie-Christine Bouton, Martine Jandrot-Perrus
1INSERM U460, CHU X. Bichat, 75877, Paris, Cedex 18, France.
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.
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