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Title: The role of endothelial cell reactive antibodies in the development and progression of peripheral arterial disease
Author: Armitage, Jonathan
ISNI:       0000 0001 3427 4745
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2007
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Introduction: The mechanism by which a small but significant proportion of patients with peripheral arterial disease (PAD) rapidly progress to critical ischaemia and limb loss is unclear. Both experimental and clinical data suggest that endothelial cell reactive antibodies (ECRA) may play a role in the progression of PAD through activation of endothelial cells and the release of inflammatory cytokines. This thesis aims to test the hypothesis that ECRA promote the development and progression of PAD. Methods: Subjects were assessed clinically and with ankle-brachial pressure indices to allow stratification into 4 groups. Subjects with critical ischaemia (CI, n=30), stable claudication (SC, n=30), healthy age-matched controls (AMC, n=20) and young healthy controls (YHC, n=20) were studied. Results: Significantly elevated levels of antibodies to cardiolipin (CL), β2-glycoprotein I (β2GPI) and heat shock protein 90 (HSP90) were found to be present in PAD patients with the most advanced disease. The data reveal that seven patients (6CI, 1SC) had pathological levels of anti-β2GPI antibodies (anti-β2GPI>22 U/mL), seven (6CI, 1SC) had pathological levels of anti-CL antibodies (anti-CL >11 GPL/mL) and three (3CI) had pathological levels of both anti-CL and anti-β2GPI antibodies. None of these subjects in the control groups had pathological levels of either anti-CL or anti-β2GPI antibodies. 40% of CI and 10% of SC had elevated levels of anti-HSP 90 antibodies compared with the AMC. Interluekin-6 levels were significantly elevated in both SC and CI over the control group and in CI over SC. Conclusions: These data support the hypotheses that ECRA promote the development of PAD. Furthermore it is likely that the multiple endothelial cell specificities found in the critical ischaemic group may well be important in the development of accelerated atherosclerosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available