The vascular endothelium is a dynamic and metabolically active organ with numerous functions, including regulation of the coagulation cascade and local blood flow, control of fluid passage into the media, and the regulation of cell migration through the vascular intima (1, 2). These many functions are reflected in the variety of molecules expressed at the cell surface and secreted by endothelial cells (ECs). The appearance of such molecules in measurable quantities in the blood allows indirect measurement of the status of the endothelium, which can exist in various different states: resting, activated, and/or dysfunctional. Stimulation of resting endothelium (e.g., by inflammatory cytokines) results in an activation state, characterized by the up regulation of various cell adhesion molecules and procoagulant molecules. Dysfunction can be thought of as an inability of the endothelium to carry out its normal physiological functions (2, 3).
The ideal test of endothelial function would be simple, quick, and inexpensive to perform, sensitive, endothelial specific, correlated with a known disease process, and deranged in a predictable way in disease processes. In other words, it would be a reliable surrogate marker for a specific endothelial disease process. In addition, the marker would be stable enough to measure reliably in the laboratory, yet also have sufficiently rapid turnover or short half-life to provide a meaningful measure of current endothelial status. These criteria effectively remove nitric oxide (NO) from a list of useful markers because it cannot be measured directly or in a simple manner in the laboratory.