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- ALSPAC, Avon longitudinal study of parents and children
- EPC, endothelial progenitor cell
- FMD, flow mediated dilation
- NO, nitric oxide
Atherosclerosis is a chronic vascular inflammatory disease, characterised by lipid accumulation, and cellular infiltration and proliferation in the arterial wall. Vascular endothelial dysfunction plays a critical role in the initiation and progression of the atherosclerotic process; the development of techniques that allow detection of endothelial function and early structural vascular disease has allowed major advances in understanding the pathophysiology at all stages of the disease process. Clinical investigation of endothelial function in children and young adults is informative. Postmortem studies demonstrating the presence of atherosclerotic lesions from as early as the first decade of life have shown that disease burden is directly associated with the extent of exposure to conventional risk factors, even at this early stage.1 Longitudinal studies have also demonstrated that this interaction between risk factors and abnormal arterial biology predicts adverse long term cardiovascular outcome. Furthermore, risk factors tend to cluster together and persist from childhood into later life, suggesting potential for early lifestyle and, where appropriate, pharmaceutical intervention. Study of clinical endothelial function in young subjects has confirmed an adverse early impact of both conventional and novel factors. Genetic influences can also be evaluated at this environmentally “naïve” stage of life. Understanding the determinants of early disease progression, based on objective measures of vascular phenotype, provides an opportunity for effective, evidence based preclinical intervention.
ENDOTHELIAL FUNCTION TESTING
By virtue of its location, the endothelium is optimally located to act as a signal transducer to modulate the impact of circulating influences on the vascular wall. Endothelium derived molecules regulate vasomotor tone, cell adhesion, coagulation, inflammation, and permeability, all of which are central to the atherogenic process. Many circulating endothelium derived adhesion molecules (for example, VCAM-1, ICAM-1, and E-selectin), coagulation factors (for example, von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1), and vasoactive mediators (for example, endothelin, prostanoids, …
Dr Halcox and Professor Deanfield are supported by the British Heart Foundation
Neither author has any relevant conflict of interest to declare