Endothelin-1 and atherosclerosis: potential complications associated with endothelin-receptor blockade.
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 (ET(A) and ET(B)). Mixed ET(A/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.
Dashwood
Michael R
MR
Department of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, Royal Free Campus, Pond Street, London NW3 2QG, UK. mdashwood@rcf.ucl.ac.uk
Tsui
Janice C S
JC
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D044022:Receptor, Endothelin A
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A