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136 | Chapter 8 initial process for neutralising and eliminating these toxic particles. 35 The complement system is also thought to contribute to endothelial dysfunction, and is activated in early fatty streaks and late stages of atherosclerosis. 38 In the present study, we have shown that both C4B and C1BQ are excellent predictors of CAD. However, once again it was the absence of both of these proteins in the FH + CAD group compared to the FH group that was predictive. While inflammation plays a key role in atherosclerosis, it is also possible that chronic exposure to stressors and inflammatory markers in the arterial wall may lead to a loss of immune homeostasis. As such, both C4B and C1BQ may play a role in the early, subclinical stages of CAD (the asymptomatic groups) when atherosclerosis is first developing, but are absent in the FH + CAD group where disease is established. Supporting this is the suggestion that the complement system has a dual role in atherosclerosis, including the removal of debris as well as amplification of the inflammatory response. Furthermore, some components of the complement system, including C1Q appear to have a protective effect. 38 Clearly the role of the complement system in the development of atherosclerosis is complex and the role of these proteins in disease progression warrants further investigation. CD14, or monocyte differentiation antigen, is a protein expressed in monocytes and macrophages and also involved in inflammation. 39 A recent study has shown that CD14 may be a potential marker of CAD where urinary CD14 levels were significantly higher in patients with angiographic CAD compared with controls. 39 Interestingly, we saw no detectable amounts of circulating CD14 in >75% of our participants, including none of the patients in the FH + CAD group. This is in contrast to the previous study, however it should be noted that we did not perform CD14 analysis on urine within our study population. In the previous study, the authors noted no significant differences in plasma CD14 between their two groups. Furthermore, while their CAD group had angiographically proven CAD, they had not had a previous coronary event. 39 The lack of association between any of the protein biomarkers and classical risk factors of CAD is interesting. Furthermore, while most of the proteins were excellent to good predictors of CAD, they were less robust as predictors of coronary atherosclerosis. The reason for this is unclear. However, it may be in part due to the fact that one or more proteins play different roles at different stages of the development of atherosclerosis. Our findings suggest that the proteins identified as potential biomarkers may be more relevant at the preclinical stage of disease development, which is where they would have the greatest clinical utility. Future studies examining healthy control populations as well as protein levels and disease progression in FH patients are needed to tease out