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Regulation of CYP27A1 in vitro and in vivo; possible implications on cellular cholesterol efflux and atherosclerosis

English title Regulation of CYP27A1 in vitro and in vivo; possible implications on cellular cholesterol efflux and atherosclerosis
Applicant Escher Geneviève
Number 106128
Funding scheme Marie Heim-Voegtlin grants
Research institution Respiratory Medicine Department Universitätsklinik Inselspital
Institution of higher education University of Berne - BE
Main discipline Cardiovascular Research
Start/End 01.11.2004 - 31.10.2006
Approved amount 250'600.00
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All Disciplines (2)

Discipline
Cardiovascular Research
Endocrinology

Keywords (6)

CYP27A1; atheriosclerosis; cholesterol efflux; xenobiotics; in vivo footprinting; methylation

Lay Summary (English)

Lead
Lay summary
CYP27A1, a mitochondrial enzyme of the cytochrome P450 family, catalysesthe conversion of cholesterol to 27-hydroxycholesterol and3-beta-hydroxy-5-cholestenoic acid. CYP27A1 is involved in bile acidssynthesis, activation of vitamin D3 and regulation of cholesterolhomeostasis. Mutation and activity loss of CYP27A1 in patients withcerebrotendinous xanthomatosis leads to reduced formation of bile acidsand cholesterol accumulation in tissues, classical parameters ofdeficiency in reverse cholesterol transport.
In this work we will investigate the effect of different xenobiotics onthe expression of CYP27A1 in human cell lines and their impact oncholesterol efflux. We will also study the regulatory elements of CYP27A1by in vivo footprinting. Finally, methylation analysis of DNA extractedfrom monocytes of atherosclerotic patients will be analysed.
Understanding the intrinsic regulatory mechanisms of CYP27A1 andmodulation of its activity towards removal of cholesterol from cells mightbear the potential of developing new therapies in atherosclerosis.
Direct link to Lay Summary Last update: 21.02.2013

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