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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Monomeric C-reactive protein and Notch-3 co-operatively increase angiogenesis through PI3K signalling pathway
Cytokine, Volume 69, No. 2, Year 2014
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Description
C-reactive protein (CRP) is the most acute-phase reactant serum protein of inflammation and a strong predictor of cardiovascular disease. Its expression is associated with atherosclerotic plaque instability and the formation of immature micro-vessels. We have previously shown that CRP upregulates endothelial-derived Notch-3, a key receptor involved in vascular development, remodelling and maturation. In this study, we investigated the links between the bioactive monomeric CRP (mCRP) and Notch-3 signalling in angiogenesis. We used in vitro (cell counting, wound-healing and tubulogenesis assays) and in vivo (chorioallantoic membrane) angiogenic assays and Western blotting to study the angiogenic signalling pathways induced by mCRP and Notch-3 activator chimera protein (Notch-3/Fc). Our results showed an additive effect on angiogenesis of mCRP stimulatory effect combined with Notch-3/Fc promoting bovine aortic endothelial cell (BAEC) proliferation, migration, tube formation in MatrigelTM with up-regulation of phospho-Akt expression. The pharmacological blockade of PI3K/Akt survival pathway by LY294002 fully inhibited in vitro and in vivo angiogenesis induced by mCRP/Notch-3/Fc combination while blocking Notch signalling by gamma-secretase inhibitor (DAPT) partially inhibited mCRP/Notch-3/Fc-induced angiogenesis. Using a BAEC vascular smooth muscle cell co-culture sprouting angiogenesis assay and transmission electron microscopy, we showed that activation of both mCRP and Notch-3 signalling induced the formation of thicker sprouts which were shown later by Western blotting to be associated with an up-regulation of N-cadherin expression and a down-regulation of VE-cadherin expression. Thus, mCRP combined with Notch-3 activator promote angiogenesis through the PI3K/Akt pathway and their therapeutic combination has potential to promote and stabilize vessel formation whilst reducing the risk of haemorrhage from unstable plaques. © 2014 Elsevier Ltd.
Authors & Co-Authors
Boras, Emhamed
United Kingdom, Manchester
Manchester Metropolitan University
Slevin, Mark A.
United Kingdom, Manchester
Manchester Metropolitan University
Alexander, M. Yvonne
United Kingdom, Manchester
Manchester Metropolitan University
United Kingdom, Manchester
The University of Manchester
Aljohi, Ali
United Kingdom, Manchester
Manchester Metropolitan University
Gilmore, William
United Kingdom, Manchester
Manchester Metropolitan University
Ashworth, Jason J.
United Kingdom, Manchester
Manchester Metropolitan University
Krupiński, Jerzy A.
United Kingdom, Manchester
Manchester Metropolitan University
Spain, Terrassa
Mutua de Terrassa
Potempa, Lawrence Albert
United States, Chicago
Roosevelt University
Al-Abdulkareem, Ibrahim
Saudi Arabia, Riyadh
National Guard Health Affairs
Elobeid, Adila
Saudi Arabia, Riyadh
National Guard Health Affairs
Matou-Nasri, Sabine
United Kingdom, Manchester
Manchester Metropolitan University
Statistics
Citations: 63
Authors: 11
Affiliations: 5
Identifiers
Doi:
10.1016/j.cyto.2014.05.027
ISSN:
10434666
e-ISSN:
10960023
Research Areas
Cancer
Noncommunicable Diseases