MRI visualized neo-intimal dissection and co-localization of novel apoptotic markers apolipoprotein C-1, ceramide and caspase-3 in a Watanabe hyperlipidemic rabbit model.

Abstract

PURPOSE:

Apoptotic arterial wall vascular smooth muscle cell death is known to contribute to plaque vulnerability and rupture. Novel apoptotic markers like apolipoprotein C-I have been implicated in apoptotic human vascular smooth muscle cell death via recruiting a neutral sphingomyelinase (N-SMase)-ceramide pathway. In vivo relevance of these observations in an animal model of plaque rupture has not been shown.

METHODS AND RESULTS:

Using Watanabe rabbits, we investigated three different groups (group 1, three normal Watanabe rabbits; group 2, six Watanabe rabbits fed with high cholesterol diet for 3 months; group 3, five Watanabe rabbits with similar diet but additional endothelial denudation). We followed progression of atherosclerosis to pharmacologically induced plaque rupture non-invasively using novel 3D magnetic resonance Fast-Field-Echo angiography (TR=7.2, TE=3.6 ms, matrix=512 x 512) and Fast-Spin-Echo vessel wall imaging methods (TR=3 heart beats, TE=10.5 ms, matrix=304 x 304) on 1.5 T MRI. MRI provided excellent image quality with good MRI versus histology vessel wall thickness correlation (r=0.8). In six animals of group 2/3 MRI detected neo-intimal dissection in the abdominal aorta which was accompanied by immuno-histochemical demonstration of concomitant aforementioned novel apoptotic markers, previously implicated in the apoptotic smooth muscle cell death in vitro.

CONCLUSIONS:

Our studies suggest a potential role for the signal transduction pathway involving apolipoprotein C-I for in vivo apoptosis and atherosclerotic plaque rupture visualized by MRI.

• Authors: Henning Steen, Antonina Kolmakova, Matthias Stuber, E Rene Rodriguez, Fabao Gao, Subroto Chatterjee, Joao A Lima
• Journal: Atherosclerosis (Atherosclerosis) Vol. 191 Issue 1 Pg. 82-9 (Mar 2007) ISSN: 0021-9150 [Print] Ireland
• PMID: 16822514 (Publication Type: Journal Article)

Chemical References

• Apolipoprotein C-I
• Biomarkers
• Ceramides
• Caspase 3

Topics

• Animals
• Aorta (metabolism, pathology)
• Apolipoprotein C-I (metabolism)
• Apoptosis (physiology)
• Atherosclerosis (physiopathology)
• Biomarkers
• Caspase 3 (metabolism)
• Ceramides
• Disease Models, Animal
• Hyperlipidemias (pathology)
• Magnetic Resonance Angiography
• Myocytes, Smooth Muscle (metabolism, pathology)
• Rabbits
• Rupture
• Signal Transduction
• Tunica Intima (pathology)