Clinical Implications of a Sandwich Enzyme Immunoassay for Big Endothelin-1

Endothelin (ET) is an endothelial-derived peptide that exerts potent vasoconstrictive activity in vivo and in vitro. An increasing body of evidence suggests that ET may have a significant role in the pathophysiological processes leading to cardiovascular disease states. Although it is not certain at this point whether ET is primarily responsible for initiating these events, sufficient evidence exists to conclude that ET is involved as a mediator or cofactor in these disease states.ET was first described by Yanagisawa et al. in 1988 (1). The pre-propeptide is cleaved to form big ET (39 amino acids) and then is further cleaved by an endothelin-converting enzyme (ECE) to form the 21-amino acid active peptide. Three pharmacologically distinct isopeptides (ET-1, ET-2, and ET-3) exist, derived from three different pre-propeptides that are encoded by separate genes (2). The ET-1 isopeptide is primarily responsible for the observed vasomotor effects. Two distinct ET receptors exist: ET-A and ET-B, the latter being associated with both vasoconstrictive and vasodilatory effects (3). In addition to its vasoactive effects, ET has been shown to affect cellular proliferation.Endothelial cells form a single-cell-thick layer that lines the entire vasculature. The continuous production and release of endothelin from the endothelial cells underscores the significant role of this peptide in the regulation of vascular tone and growth in both physiological and pathophysiological states. ET-1 has been implicated in the pathogenesis of numerous disease processes, particularly cardiovascular diseases. Significant ongoing research …