Endothelial function and atherogenesis
It is now realized that the vascular endothelium is the key signal transducer for the disturbed vascular biology that drives atherogenesis. Endothelial dysfunction leads to a pro-coagulant, adhesive, proliferative constrictor phenotype. Inflammation, endothial dysfunction and structural arterial wall changes are already linked by the end of the first decade of life. Classical risk factor burden affects nitric oxide dependent endothelial function and novel influences such as mental stress and childhood infection may produce transient endothelial dysfunction.
A large population based study of 8000 well characterized pre-pubertal- children has been undertaken to define genetic and environmental influences that drive the initiation and progression of early atherosclerosis. Endothelial dysfunction can be reversed by lifestyle intervention such as diet and exercise as well as by drugs such as statin. The ability to make objective measurements during the long pre-clinical phase of disease should permit development of an 'evidence-based' preventative program.