Endothelin--role in vascular disease.
It is now two decades since it was demonstrated that ET-1 is one of the most powerful vasoconstrictors in biology. ET-1 mediates its effects through two membrane G-protein coupled receptors, ET(A) and ET(B), which exhibit a wide tissue distribution including the endothelial cells, vascular smooth muscle cells and adventitial fibroblasts. In recent years, ET-1 has been identified as a key player of endothelial dysfunction in various cardiovascular, autoimmune and CTDs. Endothelial dysfunction results from endothelial cell injury subsequently leading to the generation of an inflammatory process and endothelial cell activation. Thus, beyond its known 'classical' vasoactive effects, ET-1 is additionally considered to be an important mediator in vessel remodelling ultimately leading to major changes in cellular and tissue architecture; it also appears to function in conjunction with other growth factors and cytokines. Consequently, ET-1 receptor antagonists may be useful in ameliorating progression of vascular dysfunction and vascular disease due to their ability to negatively modulate vasoconstrictor pathways, cytokines and inflammatory markers production, and growth factor effects. This review briefly summarizes the current knowledge on the role of ETs in vascular dysfunction and vascular disease, with a particular emphasis on ET-1 in CTDs.
Abraham
D
D
Department of Medicine, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, London, UK. d.abraham@medsch.ucl.ac.uk
Dashwood
M
M
D019332:Endothelin-1 / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014652:Vascular Diseases / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology
D019332:Endothelin-1; D017466:Receptors, Endothelin; D009569:Nitric Oxide