MRI detection of endothelial cell inflammation using targeted superparamagnetic particles of iron oxide (SPIO).

BACKGROUND: There 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. METHODS: The 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. RESULTS: Established 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. CONCLUSION: This 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

Serum beta-2 microglobulin level is elevated in patients with acute coronary syndrome

Background Beta-2 microglobulin (B2M) is a marker of renal dysfunction and immune activation. We previously reported that serum B2M is related to age, renal function, cardiovascular and all-cause mortality in Americans. Acute coronary syndrome (ACS) is a common cause of hospital admission and cardiovascular mortality. We tested the hypothesis that the serum level of B2M is elevated in ACS in a prospective study. Methods We recruited 167 Chinese patients (118 men and 49 women; mean age±SD, 64±13 years), of whom 88 had ACS and 79 were controls matched for age and sex. Serum B2M was measured in an accredited laboratory using a latex-enhanced immunoassay (intra-assay coefficient of variation 3.4%). Results In our patients, the serum B2M level (mean±SE) was 2.27±0.12 µg/mL. Because the upper reference level of serum B2M in our laboratory is 1.42 µg/mL, only 24 subjects (14%) had a serum B2M within the reference range. Serum B2M levels (mean±SE) were 2.52±0.21 in ACS patients and 1.99±0.06 µg/mL in controls (p=0.02). There was no significant correlation between serum B2M and troponin level. Serum B2M correlated with serum creatinine (ρ=0.62, p<0.001), age (Spearman’s ρ=0.52, p<0.001) and male gender (ρ=0.19, p=0.01). Conclusions Serum B2M level is increased in ACS patients. It is also related to age and gender, and the serum level of creatinine but not troponin. Our study shows for the first time that serum B2M is a cardiovascular risk marker in Chinese as it is in Americans. B2M is an established prognostic marker in multiple myeloma and so the test is widely available. A prospective study with long follow-up is warranted to evaluate B2M as a prognostic marker after ACS

Imaging vulnerable plaques by targeting inflammation in atherosclerosis using fluorescent-labeled dual-ligand microparticles of iron oxide and magnetic resonance imaging.

OBJECTIVE: Identification of patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and a prelude to clinical sequelae. There are currently no clinical imaging tools to assess the inflammatory activity within plaques. This study characterized inflammation in atherosclerosis using dual-targeted microparticles of iron oxide (DT-MPIO) as a magnetic resonance imaging (MRI) probe. METHODS: DT-MPIO were used to detect and characterize inflammatory markers, vascular cell adhesion molecule 1 (VCAM-1). and P-selectin on (1) tumor necrosis factor-α-treated cells by immunocytochemistry and (2) aortic root plaques of apolipoprotein-E deficient mice by in vivo MRI. Furthermore, apolipoprotein E-deficient mice with focal carotid plaques of different phenotypes were developed by means of periarterial cuff placement to allow in vivo molecular MRI using these probes. The association between biomarkers and the magnetic resonance signal in different contrast groups was assessed longitudinally in these models. RESULTS: Immunocytochemistry confirmed specificity and efficacy of DT-MPIO to VCAM-1 and P-selectin. Using this in vivo molecular MRI strategy, we demonstrated (1) the DT-MPIO-induced magnetic resonance signal tracked with VCAM-1 (r = 0.69; P = .014), P-selectin (r = 0.65; P = .022), and macrophage content (r = 0.59; P = .045) within aortic root plaques and (2) high-risk inflamed plaques were distinguished from noninflamed plaques in the murine carotid artery within a practical clinical imaging time frame. CONCLUSIONS: These molecular MRI probes constitute a novel imaging tool for in vivo characterization of plaque vulnerability and inflammatory activity in atherosclerosis. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid atherosclerotic disease in the future.This study was funded by The Health and Medical Research Fund from The Food and Health Bureau, The Government of The Hong Kong Special Administrative Region. The Food and Health Bureau, The Government of The Hong Kong Special Administrative Region had no involvement in the study design; collection, analysis, and interpretation of data; manuscript writing; or the decision to submit the manuscript for publication