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Atherosclerotic Rabbits (atherosclerotic + rabbits)

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Medical Sciences	100%

Selected Abstracts

Reproducibility of black blood dynamic contrast-enhanced magnetic resonance imaging in aortic plaques of atherosclerotic rabbits

JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2010
Claudia Calcagno MD
Abstract Purpose: To investigate the short-term reproducibility of black-blood dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in atherosclerotic rabbits to evaluate the potential of this technique to be a reliable readout of plaque progression and/or regression upon therapeutic intervention. Materials and Methods: Atherosclerotic rabbits were imaged at baseline and 24 hours later with DCE-MRI on a 1.5T MRI system. DCE-MRI images were analyzed by calculating the area under the signal intensity versus time curve (AUC). Intraclass correlation coefficients (ICCs) were used to evaluate interscan, intraobserver, and interobserver reproducibility. In addition, the test,retest coefficient of variation (CoV) was evaluated. Results: Statistical analyses showed excellent interscan, intraobserver, and interobserver agreement. All ICCs were greater than 0.75, P < 0.01 indicating excellent agreement between measurements. Conclusion: Experimental results show good interscan and excellent intra- and interobserver reproducibility, suggesting that DCE-MRI could be used in preclinical settings as a read-out for novel therapeutic interventions for atherosclerosis. This preliminary work encourages investigating the reproducibility of DCE-MRI also in clinical settings, where it could be used for monitoring high-risk patients and in longitudinal clinical drug trials. J. Magn. Reson. Imaging 2010;32:191,198. © 2010 Wiley-Liss, Inc. [source]

Nitric oxide selectively depletes macrophages in atherosclerotic plaques via induction of endoplasmic reticulum stress

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2007
W Martinet
Background and purpose: Macrophages in atherosclerotic plaques have a tremendous impact on atherogenesis and plaque destabilization. We previously demonstrated that treatment of plaques in cholesterol-fed rabbits with the nitric oxide (NO) donor molsidomine preferentially eliminates macrophages, thereby favouring features of plaque stability. In this study, we investigated the underlying mechanism. Experimental approach: Macrophages and smooth muscle cells (SMCs) were treated in vitro with the NO donors, spermine NONOate or S -nitroso- N -acetylpenicillamine (SNAP) as well as with the well-known endoplasmic reticulum (ER) stress inducers thapsigargin, tunicamycin, dithiothreitol or brefeldin A. Cell viability was analysed by Neutral Red viability assays. Cleavage of caspase-3, DNA fragmentation and ultrastructural changes were examined to characterize the type of macrophage death. Induction of ER stress was evaluated by measuring C/EBP homologous protein (CHOP) expression, phosphorylation of eukaryotic initiation factor 2, (eIF2a), splicing of X-box binding protein 1 (XBP1) and inhibition of protein synthesis. Key results: Macrophages and SMCs treated with spermine NONOate or SNAP showed several signs of ER stress, including upregulation of CHOP expression, hyperphosphorylation of eIF2,, inhibition of de novo protein synthesis and splicing of XBP1 mRNA. These effects were similar in macrophages and SMCs, yet only macrophages underwent apoptosis. Plaques from molsidomine-treated atherosclerotic rabbits showed a 2.7-fold increase in CHOP expression as compared to placebo. Beside NO, selective induction of macrophage death could be initiated with thapsigargin and tunicamycin. Conclusions and implications: Induction of ER stress explains selective depletion of macrophages in atherosclerotic plaques by a NO donor, probably via inhibition of protein synthesis. British Journal of Pharmacology (2007) 152, 493,500; doi:10.1038/sj.bjp.0707426; published online 13 August 2007 [source]