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Endothelial function: 20 years of clinical investigation
  1. P Vallance
  1. Correspondence to:
    Professor Patrick Vallance
    BHF Laboratories, Division of Medicine, University College London, London W1P 9LN, UK;

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In 1980 Furchgott and Zawadzki described the phenomenon of endothelium dependent relaxation1 and identified a novel labile relaxant factor later identified as nitric oxide. A few years earlier John Vane and colleagues2 had identified prostacyclin as a potent antiplatelet agent released from endothelial cells. Together these findings stimulated a huge increase in clinical research in vascular mechanisms and endothelial function. Twenty years on it is time to take stock.

The three articles in this mini-symposium place the research on endothelial function in a clinical context. Deanfield and Halcox outline the evidence that changes in endothelium dependent relaxation can be detected even in children and that this may represent the very earliest changes that ultimately lead to atherosclerosis. Hingorani takes this discussion into the realms of nature versus nurture debate by identifying the potential impact of genetic variations in determining key aspects of endothelial function. Finally, Vita addresses the question of whether measures of endothelium dependent relaxation are predictive of cardiovascular events, how changes in more accessible vascular beds such as the forearm relate to changes in the heart, and whether there is a realistic possibility that measures of endothelial function will have a place in the clinic.

Three other areas are emerging that are not covered in detail but warrant consideration. The first is the question of whether circulating endothelial progenitor cells are important in repair processes and to what extent they determine vascular health. The second is the variable use of the term “endothelial function” that is used and understood differently by different individuals; it is increasingly clear that there are so many different functions of the endothelium that the catch-all term may no longer be appropriate. The third relates to the recent observations that endothelium dependent relaxation varies widely within individuals from day to day dependent on other factors such as the state of systemic inflammation3 or even in response to mental stress.4 It seems that as endothelial biology is becoming very much part of mainstream cardiology there is still more that we do not know than there is that we do know.