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 × 512) and Fast-Spin-Echo vessel wall imaging methods (TR = 3 heart beats, TE = 10.5 ms, matrix = 304 × 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.
Original language | English (US) |
---|---|
Pages (from-to) | 82-89 |
Number of pages | 8 |
Journal | Atherosclerosis |
Volume | 191 |
Issue number | 1 |
DOIs | |
State | Published - Mar 2007 |
Keywords
- Apoptosis
- Atherosclerosis
- Inflammation
- NMR
- Smooth muscle cells
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine