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

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

doi:10.1016/j.atherosclerosis.2006.05.022

« Previous Next »Atherosclerosis
Volume 191, Issue 1 , Pages 82-89, March 2007

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
- Department of Cardiology, University of Heidelberg, Germany
- These authors contributed equally to this work.
Antonina Kolmakova
- Department of Pediatrics, Johns Hopkins University, Baltimore, USA
- These authors contributed equally to this work.
Matthias Stuber
- Department of Radiology, Johns Hopkins University, Baltimore, USA
E Rene Rodriguez
- Department of Pathology, Johns Hopkins University, Baltimore, USA
Fabao Gao
- Department of Radiology, Johns Hopkins University, Baltimore, USA
Subroto Chatterjee
- Department of Pediatrics, Johns Hopkins University, Baltimore, USA
- These corresponding authors contributed equally to this work.
- Correspondence to (Biochemistry): Department of Pediatrics at Johns Hopkins and the Department of Biochemistry, National University of Singapore, Room 312, 550 North Broadway, USA. Tel.: +1 410 614 2518; fax: +1 410 614 2826.
Joao A. Lima
- Department of Cardiology, University of Heidelberg, Germany
- These corresponding authors contributed equally to this work.
- Correspondence to (MRI): 600 N Wolfe Street, Blalock 524D1, Baltimore, MD 21287, United States. Tel.: +1 410 614 1284; fax: +1 410 614 8222.

Received 16 August 2005; received in revised form 24 April 2006; accepted 3 May 2006. published online 07 July 2006.

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=3.6ms, matrix=512×512) and Fast-Spin-Echo vessel wall imaging methods (TR=3 heart beats, TE=10.5ms, matrix=304×304) on 1.5T 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.

Keywords: Apoptosis, Atherosclerosis, NMR, Smooth muscle cells, Inflammation