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

DOI: 10.1186/1471-2121-9-47

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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 μg/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).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.Atherosclerosis is the underlying cause of ischemic cardiovascular and cerebrovascular diseases [1-3]. Unstable carotid atherosclerotic plaques can undergo thrombotic complications and trigger acute clinical events [4-6]. In atherosclerotic plaques angiogenesis allows the formation of new microvessels to maintain oxygen and nutrient supply for vascular cells. Such processes are potenciated by different molecules secreted by vascular and inflammatory cells [5]. Neovessel growth occurs in active regions of atherosclerotic lesions undergoing remodelling. Our previous studies have demonstrated specific molecular deregulation occurring in these regions, consistent with the promotion of angiogenesis. The new vessels of atherosclerotic lesions may be a focus of instability, since they facilitate the infiltration of inflammatory cells and due to their tendency to leak,


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