Exaggerated postprandial lipaemia has been implicated in the development of atherosclerosis. Thus, by reducing postprandial TAG concentrations, exercise may play a role in delaying atherogenic progression. This thesis sought to explore the qualitative nature of, and the mechanisms behind, the moderate exercise-induced attenuation to postprandial lipaemia. Before the experimental studies commenced, a reproducibility study was undertaken. This showed that in a group of eight middle-aged men, the postprandial plasma TAG response differed by only 1.9 ± 5.1 % (mean ± standard error) on a testretest basis, indicating that the oral fat tolerance test had enough precision to detect the effect of exercise on TAG metabolism. Previous work suggested that the exercise-induced reduction to lipaemia was linked to the energy expended by exercise. As the attenuation may have been mediated by energy deficit, rather than exercise per se, a study comparing the effect of a 90-minute moderate exercise session with an equivalent dietary-induced energy deficit on postprandial lipid metabolism was undertaken, in a group of eleven postmenopausal women. This showed that the reduction in postprandial lipaemia elicited by exercise was far greater than that elicited by intake-restriction (20 % vs. 7 %). The second experimental study aimed to establish the effect of a 90-minute moderate exercise session on postprandial chylomicron- and very-Iow-density lipoprotein (VLDL)-TAG concentrations, and its effect on exogenous (through use of a l3e-Iabelled lipid) and endogenous fat oxidation, in a group oftwelve middle-aged men. Exercise reduced postprandial lipaemia by 23 %, and over three-quarters of this reduction was due to lower VLDL-TAG concentrations. Increases in endogenous fat oxidation accounted for over half of the increase in postprandial fat oxidation. In the third experimental study, the effect of a 90-minutes moderate exercise session on Intralipid clearance, and postprandial lipaemia, was determined in a group of eight middle-aged men. Exercise attenuated postprandial lipaemia by 18 %, but did not increase Intralipid clearance. Taken together, these data imply that moderate exercise predominantly reduced postprandial TAG concentrations by reducing hepatic VLDL secretion, rather than increasing TAG clearance, and this effect is not mediated by whole-body energy deficit. In addition, this work has shown that moderate exercise is effective at attenuating postprandial lipaemia in middle-aged men and postmenopausal women.

Background: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterised by autoantibody production and variable clinical features, ranging from mild to severe disease. Patients with SLE are at increased risk of developing accelerated atherosclerosis. Biomarkers have potential utility in SLE as markers of disease or predictors of future clinical events and mortality. Objective The aim of this thesis was to identify serological biomarkers predictive for erosive arthritis (EA), cardiovascular events (CVEs), mortality and subclinical atherosclerosis in SLE. Methods: In chapters 2 to 4, study subjects were SLE patients from Bath. Anti-cyclic citrullinated peptide antibodies (ACPA) and HLA-DR and -DQ were studied for markers of EA, and anticardiolipin (aCL) and lipoprotein profiles for markers of CVEs and mortality. In chapters 5 and 6, study subjects were women with SLE from Manchester. B-mode ultrasound scans of subjects' carotid arteries were performed at baseline and follow-up time-points to detect atherosclerotic plaque. Baseline IgG and IgM antiphospholipid (aPL) antibodies and CV risk factors were studied for markers of subclinical atherosclerosis. Clinical data collected for all studies included SLE features and auto-antibody profiles. Results: ACPA was identified as a marker of a SLE phenotype with EA - "rhupus". Patients with major erosive arthritis were HLA-DQB1*0302 carriers. Increased aCL GPL levels and total cholesterol : high density lipoprotein-C (TC : HDL-C) ratio were markers for future CVEs, and increased TC : HDL ratio, aCL GPL and lipoprotein(a) concentrations were markers for increased mortality. Lower HDL-C concentrations and anti-annexin A5 (anti-AnxA5) GPL were markers of carotid plaque progression. Conclusion: This thesis identified new markers for EA, subclinical atherosclerosis and future CVE and mortality risk in SLE. Strategies to incorporate these new CV markers into clinical CV risk assessments may assist in distinguishing the subset of SLE patients most at risk of developing accelerated atherosclerosis.

Background: Atherosclerosis is considered a chronic inflammation of arterial vessels with the involvement of several immune cells causing severe cardiovascular diseases. Lipoprotein apheresis (LA) improves cardiovascular conditions of patients with severely disturbed lipid metabolism. In this context, little is known about the impact of LA on various immune cell populations, especially over time. Methods: Immune cells of 18 LA-naïve patients starting weekly LA treatment were analyzed before and after four apheresis cycles over the course of 24 weeks by flow cytometry. Results and Conclusions: An acute lowering effect of LA on T cell and natural killer (NK) cell subpopulations expressing CD69 was observed. The nonclassical and intermediate monocyte subsets as well as HLA-DR+ 6-sulfo LacNAc+ monocytes were significantly reduced during the apheresis procedure. We conclude that LA has the capacity to alter various immune cell subsets. However, LA has mainly short-term effects than long-term consequences on proportions of immune cells.