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Role of CYP27A1 in reverse cholesterol transport and atherosclerosis in vivo

English title Role of CYP27A1 in reverse cholesterol transport and atherosclerosis in vivo
Applicant Escher Geneviève
Number 109774
Funding scheme Project funding
Research institution Respiratory Medicine Department Universitätsklinik Inselspital
Institution of higher education University of Berne - BE
Main discipline Cardiovascular Research
Start/End 01.12.2005 - 30.11.2008
Approved amount 198'818.00
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Keywords (5)

CYP27A1; atherosclerosis; reverse cholesterol transport; adenovirus; CYP27A1/apoE double knockout mouse

Lay Summary (English)

Lead
Lay summary
The development of an atherosclerotic plaque is a decade lasting event. It starts with the lesions which may occur already in the adolescence, its progression is dependant on gender, genetics and environmental factors.One of the key elements in the pathogenesis of atherosclerosis is the accumulation of cholesterol. Therefore, treatments targeting pathways of cholesterol delivery to and removal from the cells are a promising tool towards the prevention and treatment of atherosclerosis.
We have previously shown in two different cell lines (CHOP and RAW 264.7) that CYP27A1 overexpression enhances the first step of reverse cholesterol transport, cholesterol efflux.
The aim of this project is to study the exact role of CYP27A1 in reverse cholesterol transport and its contribution to the formation/dissolution of the atherosclerotic plaque.
For that purpose, we w ill cross the already well described CYP27A1/ko mouse with the apoE/ko mouse, a unique model that features the atherosclerotic lesions similar to that found in humans. As a result we will generate the double knock out mouse CYP27A1/apoE dko. We will then analyse the contribution of CYP27A1 towards reverse cholesterol transport in vivo by quantifying the egress of labelled cholesterol from intraperitoneally injected macrophages and its appearance in plasma, liver, lungs and faeces. The development of the atherosclerotic plaque will be quantified with red O staining of segments of the proximal aorta in the same group of animals. Restitution of CYP27A1 activity will be performed in the CYP27A1/apoE dko by injecting intravenously the adenovirus expressing CYP27A1 (Av5-CYP27A1) that I have previously constructed and its effect on in vivo reverse cholesterol transport and atherosclerotic plaque formation will be analysed.
This project should clarify the role of CYP27A1 in the regulation of cholesterol removal from the cells in vivo and quantify its anti-atherosclerotic contribution in the atherosclerotic mouse model.Development of stents coated with Av5-CYP27A1 might be a promising strategy to avoid restenosis following artery dilatations with stent implantation in the treatment of coronary diseases.
Direct link to Lay Summary Last update: 21.02.2013

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Number Title Start Funding scheme
122133 Role of CYP27A1 expression in reverse cholesterol transport and atherosclerosis in an atherosclerotic mouse model 01.12.2008 Project funding

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