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Date of Award

4-1978

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Engineering

Supervisor

F.P. Bell

Abstract

Arterial and plasma carnitine metabolism was investigated in normal and atherosclerotic rabbits. Atherogenic cholestrol-supplemented diets induced hypercholesterolemia in rabbits; hypercholesterolemia was associated with hypercarnitinemia and increased levels of carnitine and acylcarnitines in atherosclerotic aortas. Carnitine derived from the bloodstream started to accumulate in aortas of animals fed cholesterol-supplemented diets before the development of gross atherosclerotic lesions; this response of the aorta to hypercholesterolemia and hypercarnitinemia was not shared by the heart. Carnitine palmitoyltransferase (CPT), a key enzyme in fatty acid metabolism, was also investigated in normal and atherosclerotic aortas. CPT activity was associated with mitochondrial and microsomal fractions isolated from rabbit aortas. The location of CPT activity in the aorta differed from that reported for heart and liver; in these tissues, CPT activity is exclusively mitochondrial. Arterial CPT activity was not affected by the addition of cholesterol to the animal's diet. It is hypothesized that acyl-CoA in atherosclerotic tissue is predominantly esterified to carnitine rather than to glycerol-3-phosphate; supporting this hypothesis was the observation that long-chain acylcarnitines increased in atherosclerotic aortas. The hypothesis offers an explanation for several biochemical changes that occur in fatty acid metabolism in atherosclerosis.

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