IMR Press / FBL / Volume 13 / Issue 8 / DOI: 10.2741/2895

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Vascular effects of thrombin: involvement of NOR-1 in thrombin-induced mitogenic stimulus in vascular cells
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1 Centro de Investigacion Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, c/Antoni Mª Claret 167, 08025 Barcelona, Spain

*Author to whom correspondence should be addressed.


Front. Biosci. (Landmark Ed) 2008, 13(8), 2909–2915;
Published: 1 January 2008

Neuron-derived orphan receptor-1 (NOR-1) is a nuclear receptor recently involved in the onset and development of atherosclerosis. NOR-1 is induced in a cell-specific manner by extracellular stimuli. NOR-1 is over-expressed in human atherosclerotic plaques and in porcine arteries subjected to angioplasty, is induced by growth factors in vascular cells and it has been involved in cell migration and proliferation. This article examines the mechanisms that regulate NOR-1 in vascular cells and the effects of NOR-1 knockdown on cell growth induced by mitogens, in particular thrombin. Mitogenic stimuli up-regulates NOR-1 in endothelial cells (ECs) through multiple pathways, including increase of cytosolic calcium, activation of protein kinase C, mitogen-activated protein kinase (MAPK) (ERK1/2 and p38 MAPK) and downstream activation of cAMP response element binding protein (CREB). Inhibition of protease-activated receptor-1 (PAR-1) abolished thrombin-induced NOR-1 up-regulation and DNA synthesis. NOR-1 knockdown reduces DNA synthesis and EC re-growth in an in vitro model of wound repair. NOR-1 could be regarded as a new target to prevent endothelial effects triggered by thrombin and other mitogens.

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