Abstract
BackgroundThere is currently no clinical imaging technique available to assess the degree of inflammation associated with atherosclerotic plaques. This study aims to develop targeted superparamagnetic particles of iron oxide (SPIO) as a magnetic resonance imaging (MRI) probe for detecting inflamed endothelial cells.MethodsThe in vitro study consists of the characterisation and detection of inflammatory markers on activated endothelial cells by immunocytochemistry and MRI using biotinylated anti-P-selectin and anti-VCAM-1 (vascular cell adhesion molecule 1) antibody and streptavidin conjugated SPIO.ResultsEstablished an in vitro cellular model of endothelial inflammation induced with TNF-α (tumor necrosis factor alpha). Inflammation of endothelial cells was confirmed with both immunocytochemistry and MRI. These results revealed both a temporal and dose dependent expression of the inflammatory markers, P-selectin and VCAM-1, on exposure to TNF-α.ConclusionThis study has demonstrated the development of an in vitro model to characterise and detect inflamed endothelial cells by immunocytochemistry and MRI. This will allow the future development of contrast agents and protocols for imaging vascular inflammation in atherosclerosis. This work may form the basis for a translational study to provide clinicians with a novel tool for the in vivo assessment of atherosclerosis.
Highlights
There is currently no clinical imaging technique available to assess the degree of inflammation associated with atherosclerotic plaques
Increased levels of P‐selectin and VCAM‐1 in activated Mouse aortic endothelial cells (mAEC) P-selectin and vascular cell adhesion molecule-1 (VCAM-1) were only detected in activated mAEC as shown by the red fluorescence signal at various concentrations of tumour necrosis factor-α (TNF-α) and incubation periods, whilst no expression was observed in the untreated control cells (Figs. 3a, 4a)
The dose response of TNF-α in mAEC was similar as detected by P-selectin and VCAM-1
Summary
There is currently no clinical imaging technique available to assess the degree of inflammation associated with atherosclerotic plaques. One of the earliest events in atherosclerosis is the over-expression of adhesion molecules on the activated endothelium following exposure to inflammatory cytokines [7] These pathophysiologically ‘inducible’ endothelial adhesion molecules, such as VCAM-1 (vascular cell adhesion molecule-1) and P-selectin, have the potential to serve as attractive biomarkers for imaging inflammation in atherosclerosis. P-selectin (CD62P, GMP-140, PADGEM), a single-chain glycoprotein, is an adhesion molecule expressed on the surface of activated endothelial cells, which line the luminal surface of blood vessels, and on activated platelets [10]. It mediates initial leukocyte rolling, preceding leukocyte diapedesis into the atherosclerotic lesions [10, 11]. These features render VCAM-1 and P-selectin an ideal biomarker for functional molecular imaging and targeted therapeutics in early atherosclerosis
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