6 research outputs found
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Using a Systems Pharmacology Approach to Study the Effect of Statins on the Early Stage of Atherosclerosis in Humans
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
Mathematical modelling of atheroma plaque formation and development in coronary arteries
Permeation of human plasma lipoproteins in human carotid endarterectomy tissues: measurement by optical coherence tomography
Atherosclerosis is an inflammatory process occurring in arterial tissue, involving the subintimal accumulation of LDL. Measurement of the rate at which LDL and other lipoproteins, such as HDL and VLDL, enter and exit the tissue can provide insight into the mechanisms involved in the development of atherosclerotic lesions. Permeation of VLDL, LDL, HDL, and glucose was measured for both normal and atherosclerotic human carotid endarterectomy tissues (CEA) at 20°C and 37°C using optical coherence tomography (OCT). The rates for LDL permeation through normal CEA tissue were (3.16 ± 0.37) × 10−5 cm/s at 20°C and (4.77 ± 0.48) × 10−5 cm/s at 37°C, significantly greater (P < 0.05) than the rates for atherosclerotic CEA tissue at these temperatures [(1.97 ± 0.34) × 10−5 cm/s at 20°C and (2.01 ± 0.23) × 10−5 cm/s at 37°C]. This study effectively used OCT to measure the rates at which naturally occurring lipoproteins enter both normal and diseased carotid intimal tissue