Studies into Subclinical and Clinical Manifestations of Atherosclerosis

Atherosclerosis is the biological process resulting in several clinical cardiovascular (CV) diseases including coronary artery disease (CAD). In this thesis I aimed to investigate the (i) risk factors and biology of early atherosclerosis in adolescents and (ii) in the conversion of stable to unstable plaque in CAD provide further understanding of atherogenesis, and potentially of novel therapeutics for clinical disease presentations. In Chapters 3-5, I investigated early arterial changes, firstly, I assessed sex differences in vascular markers of atherosclerosis including Augmentation Index and Pulse Wave Velocity and the determinants of those markers of early atherosclerosis. In Chapter 4, I assessed the influence of BMI trajectory on arterial structure and function and CV risk factors contributing to atherosclerosis, identifying an early rising BMI, before 2 years of age, to adversely impact CV risk in adolescence. In Chapter 5, I investigated the role of telomeres, a marker of biological ageing, on carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis in adolescence. Chapters 6 and 7 focused on the biology of unstable atherosclerotic plaque in CAD. In Chapter 6, I investigated microparticle (MP) release pre- and post-percutaneous coronary intervention (PCI) in stable and unstable CAD. I found neutrophil-derived MP to be released into the circulation in acute coronary syndrome (ACS) patients post PCI. In Chapter 7, I sought to identify differences in circulating microRNA (miRNA) in ACS patients. I found 30 circulating miRNAs to have higher expression in ACS patients compared to controls and 12 miRNAs to be modulated by colchicine, a novel therapeutic in ACS. Taken together, these studies provide further understanding of the influences on vessels and CV risk in early life and of unstable plaque biology in CAD providing an opportunity to possibly prevent atherosclerosis and develop and utilise novel therapeutics in clinical atherosclerosis