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

Henning Steen, Antonina Kolmakova, Matthias Stuber, E. Rene Rodriguez, Fabao Gao, Subroto Chatterjee, Joao A. Lima

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)82-89
Number of pages8
JournalAtherosclerosis
Volume191
Issue number1
DOIs
StatePublished - Mar 1 2007

Keywords

  • Apoptosis
  • Atherosclerosis
  • Inflammation
  • NMR
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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