Characterisation of an atherosclerotic micro-calcification model using ApoE−/− mice and PET/CT

MacAskill, Mark G. and McDougald, Wendy and Alcaide-Corral, Carlos and Newby, David E. and Tavares, Adriana A.S. and Hadoke, Patrick W.F. and Wu, Junxi (2020) Characterisation of an atherosclerotic micro-calcification model using ApoE−/− mice and PET/CT. IJC Heart and Vasculature, 31. 100672. ISSN 2352-9067

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    Abstract

    Intraplaque calcification is a prominent feature of advanced atherosclerotic plaque development. Current clinical evidence suggests that the size of calcium deposit may confer different effects on plaque stability [1], [2], [3]. Macro-calcified deposits (CT detected) are thought to confer plaque stability whereas micro-calcification ([18F]NaF PET detected) are thought to be a feature of high-risk ‘vulnerable’ plaques which are prone to rupture. Following on from the emerging role of micro-calcification in high risk plaques within the clinic [4], there is now an urgent need for preclinical atherosclerotic models with this feature to gain mechanistic insights and assess the impact of calcification-targeted therapies. Using a combination of invasive and ex vivo methods, ApoE−/− mice placed on an atherogenic diet have been shown to develop intraplaque calcification [5]. Additionally, [18F]NaF PET/CT has been used to assess the impact of exercise on calcification in ApoE−/− mice on a western diet [6]. In this study, we set out to determine if [18F]NaF PET/CT could be used to non-invasively detect and quantify micro-calficiation in the ApoE−/− high cholesterol diet (HCD) mouse model, and examine the temporal nature of this process.