Key result
Exposure of human endothelial cells to serine proteases or PAR-selective agonists enhances COX-2 expression via pro-inflammatory signaling, regulating PAR-stimulated angiogenesis.
COX-2-derived mediators appear to be important autocrine regulators of PAR-stimulated angiogenesis in human endothelial cells, potentially linking vascular inflammation with repair.
May link inflammation to endothelial repair in vitro; leaves open clinical relevance of PAR-COX-2 targeting.
COX (cyclo-oxygenase)-2 and members of the PAR (protease-activated receptor) family (PARs 1-4) are highly overexpressed in a number of angiogenesis-dependent pathologies, including advanced atherosclerosis and cancer. An appreciation of the potential role(s) of PARs and COX enzymes in physiological angiogenesis is, however, currently lacking. Exposure of human endothelial cells to serine proteases (e.g. thrombin) or to PAR-selective agonist peptides leads to a wide range of cellular responses, including enhanced expression of COX-2, and we have shown that this induction depends on activation of classic pro-inflammatory signalling elements [e.g. MAPKs (mitogen-activated protein kinases) and NF-kappaB (nuclear factor kappaB)]. Our current studies suggest that COX-2-derived mediators are important autocrine regulators of PAR-stimulated angiogenesis. This mechanism could help us to explain how this novel family of receptors couple vascular inflammation with repair and angiogenesis in health and disease.
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Wheeler‐Jones et al. (2009) conducted a review in Angiogenesis-dependent pathologies (atherosclerosis, cancer). Serine proteases or PAR-selective agonist peptides was evaluated on COX-2 expression and angiogenesis. Exposure of human endothelial cells to serine proteases or PAR-selective agonists enhances COX-2 expression via pro-inflammatory signaling, regulating PAR-stimulated angiogenesis.
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