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Using a Systems Pharmacology Approach to Study the Effect of Statins on the Early Stage of Atherosclerosis in Humans

Pichardo-Almarza, CD; Metcalf, L; Finkelstein, A; Diaz-Zuccarini, V; (2014) Using a Systems Pharmacology Approach to Study the Effect of Statins on the Early Stage of Atherosclerosis in Humans. CPT: Pharmacometrics and Systems Pharmacology , 4 (1) , Article e7. 10.1002/psp4.7. Green open access

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Abstract

More than 100,000 people have participated in controlled trials of statins (lowering cholesterol drugs) since the introduction of lovastatin in the 80s. Meta-analyses of this data have shown that statins have a beneficial effect on treated groups compared to control groups, reducing cardiovascular risk. Inhibiting the HMG-CoA reductase in the liver, statins can reduce cholesterol levels, thus reducing LDL levels in circulation. Published data from intravascular ultrasound studies (IVUS) was used in this work to develop and validate a unique integrative system model; this consisted on analysing control groups from two randomised controlled statins trials (24/97 subjects respectively), one treated group (40 subjects, simvastatin trial) and 27 male subjects (simvastatin, pharmacokinetic study). The model allows to simulate the pharmacokinetics of statins and its effect on the dynamics of lipoproteins (e.g. LDL) and the inflammatory pathway whilst simultaneously exploring the effect of flow-related variables (e.g. wall shear stress) on atherosclerosis progression.

Type: Article
Title: Using a Systems Pharmacology Approach to Study the Effect of Statins on the Early Stage of Atherosclerosis in Humans
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/psp4.7
Publisher version: http://dx.doi.org/10.1002/psp4.7
Language: English
Additional information: © 2014 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: statins, atherosclerosis, system model, systems pharmacology
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1456306
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