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Title: The role of complement and complement regulatory proteins in the progression of atherosclerosis
Author: Lewis, Ruth D.
ISNI:       0000 0004 2751 5186
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2011
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Whilst evidence from human studies suggests that complement activation is pro-atherogenic, studies using animals models of the disease, including the low density receptor deficient (ldlr-/-) and apolipoprotein E deficient (apoE-/-) mouse models, contradict one another. The hypothesis underpinning this thesis is that the complement system contributes to disease pathology in atherosclerotic plaques of apoE-/- mice. The work focussed on the membrane attack complex (MAC) of the terminal pathway and the central component of the complement system, C3. I have shown that in the absence of the MAC regulator CD59a, apoE-/- mice had accelerated atherosclerosis compared to controls, accompanied by increased MAC activation within the plaques. In accordance, C5 deficiency was protective against atherosclerosis in apoE-/- mice, a result of absence of MAC in these mice. However, MAC inhibition using an anti-C5 antibody in apoE-/- mice did not inhibit progression of atherosclerosis. Surprisingly, in the absence of CD55, apoE-/- mice had smaller atherosclerotic lesions together with an anti-atherogenic lipoprotein profile and increased C3 activation product, C3adesArg, in their plasma. The data reveal a novel role for CD55 during lipid metabolism and, together with published data on the metabolic role of C3adesArg, highlight the need for further investigations into the role of complement during lipid metabolism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available