Lipoprotein oxidation and its significance for atherosclerosis: a mathematical approach.
Atherosclerosis is a chronic disease which involves the build up of cholesterol and fatty deposits within the arterial wall. This results in the narrowing of the vessel lumen, which eventually restricts blood flow to vital organs such as the heart and lungs. These events may culminate in a heart attack or stroke, the commonest causes of death in the U.K. population. In this paper we study the early stages of atherosclerosis which include the build up of cholesterol within subendothelial cells to form what is known as a fatty streak, the earliest identifiable evidence of atherosclerosis. The deposition of cholesterol is believed to be a consequence of oxidation of circulating cholesterol-rich lipoproteins, in particular low density lipoproteins (LDLs). Via a mathematical model we investigate this process of oxidation within the context of an in vitro framework. We first recreate existing experimental results and then extend the model to investigate phenomenon not studied by current experimental protocols. We find that the model displays hysteresis which reveals some interesting insights into possible in vivo events. Mathematical analysis of this behaviour predicts that vitamin E supplementation is not as beneficial as high density lipoproteins (HDLs) and vitamin C. Furthermore, the scavenging of oxidants by HDL can provide an important first line of defence against LDL oxidation.
Cobbold
C A
CA
Centre for Theoretical Modelling in Medicine, Department of Mathematics, Heriot-Watt University, Edinburgh EH14 4AS, U.K. C.A.Cobbold@ma.hw.ac.uk
Sherratt
J A
JA
Maxwell
S R J
SR
D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D003198:Computer Simulation; D006801:Humans; D008075:Lipoproteins, HDL / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000009:adverse effects / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D014810:Vitamin E / Q000494:pharmacology
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014810:Vitamin E; D001205:Ascorbic Acid