Affiliation: | a Department of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, Royal Free Campus, Pond Street, London NW3 2QG, UK b Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, Pond Street, London NW3 2QG, UK |
Abstract: | Atherosclerotic vascular disease remains the single most prevalent cause of death and morbidity in the western world. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that also possesses mitogenic activity on many cell types, including vascular smooth muscle cells. Raised plasma and tissue levels of ET-1 have been described in atherosclerosis in animal models and in man, suggesting that this peptide plays a pathophysiological role in this condition. Two main ET-1 receptors have been cloned (ETA and ETB). Mixed ETA/B and receptor subtype selective antagonists are now available. Since ET-1 is generally believed to be a ‘pathophysiological peptide’, we discuss the therapeutic potential of ET-1 antagonists in atherosclerosis and consider whether, at certain sites in this process, ET-1 may play a beneficial role. In such situations ET antagonism may be undesirable. |