C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression Export

@article{citeulike:3183904, abstract = {BACKGROUND:Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP) is an acute phase reactant whose expression in the vascular wall, in particular, in reactive plaque regions, and circulating levels increase in patients at high risk of cardiovascular events. Although CRP is known to induce a pro-inflammatory phenotype in endothelial cells (EC) a direct role on modulation of angiogenesis has not been established.RESULTS:Here, we show that CRP is a powerful inducer of angiogenesis in bovine aortic EC (BAEC) and human coronary artery EC (HCAEC). CRP, at concentrations corresponding to moderate/high risk (1-5 mug/ml), induced a significant increase in proliferation, migration and tube-like structure formation in vitro and stimulated blood vessel formation in the chick chorioallantoic membrane assay (CAM). CRP treated with detoxi-gel columns retained such effects. Western blotting showed that CRP increased activation of early response kinase-1/2 (ERK1/2), a key protein involved in EC mitogenesis. Furthermore, using TaqMan Low-density Arrays we identified key pro-angiogenic genes induced by CRP among them were vascular endothelial cell growth factor receptor-2 (VEGFR2/KDR), platelet-derived growth factor (PDGF-BB), notch family transcription factors (Notch1 and Notch3), cysteine-rich angiogenic inducer 61 (CYR61/CCN1) and inhibitor of DNA binding/differentiation-1 (ID1).CONCLUSION:This data suggests a role for CRP in direct stimulation of angiogenesis and therefore may be a mediator of neovessel formation in the intima of vulnerable plaques.}, author = {Turu, Marta and Slevin, Mark and Matou, Sabine and West, David and Rodriguez, Cristina and Luque, Ana and Olivares, Marta G. and Badimon, Lina and Gonzalez, Jose M. and Krupinski, Jerzy}, citeulike-article-id = {3183904}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2121-9-47}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18764931}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18764931}, day = {02}, doi = {10.1186/1471-2121-9-47}, issn = {1471-2121}, journal = {BMC Cell Biology}, keywords = {c-reactive-protein}, month = {September}, number = {1}, pages = {47+}, posted-at = {2008-09-07 22:46:53}, priority = {2}, title = {C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression}, url = {http://dx.doi.org/10.1186/1471-2121-9-47}, volume = {9}, year = {2008} }

TY - JOUR ID - citeulike:3183904 L3 - citeulike-article-id:3183904 N2 - BACKGROUND:Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP) is an acute phase reactant whose expression in the vascular wall, in particular, in reactive plaque regions, and circulating levels increase in patients at high risk of cardiovascular events. Although CRP is known to induce a pro-inflammatory phenotype in endothelial cells (EC) a direct role on modulation of angiogenesis has not been established.RESULTS:Here, we show that CRP is a powerful inducer of angiogenesis in bovine aortic EC (BAEC) and human coronary artery EC (HCAEC). CRP, at concentrations corresponding to moderate/high risk (1-5 mug/ml), induced a significant increase in proliferation, migration and tube-like structure formation in vitro and stimulated blood vessel formation in the chick chorioallantoic membrane assay (CAM). CRP treated with detoxi-gel columns retained such effects. Western blotting showed that CRP increased activation of early response kinase-1/2 (ERK1/2), a key protein involved in EC mitogenesis. Furthermore, using TaqMan Low-density Arrays we identified key pro-angiogenic genes induced by CRP among them were vascular endothelial cell growth factor receptor-2 (VEGFR2/KDR), platelet-derived growth factor (PDGF-BB), notch family transcription factors (Notch1 and Notch3), cysteine-rich angiogenic inducer 61 (CYR61/CCN1) and inhibitor of DNA binding/differentiation-1 (ID1).CONCLUSION:This data suggests a role for CRP in direct stimulation of angiogenesis and therefore may be a mediator of neovessel formation in the intima of vulnerable plaques. IS - 1 JF - BMC Cell Biology SN - 1471-2121 TI - C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression VL - 9 SP - 47 KW - c-reactive-protein AU - Turu, Marta AU - Slevin, Mark AU - Matou, Sabine AU - West, David AU - Rodriguez, Cristina AU - Luque, Ana AU - Olivares, Marta AU - Badimon, Lina AU - Gonzalez, Jose AU - Krupinski, Jerzy PY - 2008/09/02/ UR - http://dx.doi.org/10.1186/1471-2121-9-47 ER -