Endothelium-dependent hyperpolarization as a remote anti-atherogenic mechanism.
Endothelial cell injury and the loss of cytoprotective mechanisms that involve nitric oxide, prostacyclin and endothelium-dependent hyperpolarization (EDH) are thought to underlie atherosclerosis, although how these mechanisms are anti-atherogenic is unclear. This is particularly so because thrombus formation, one of the major initiators of the disease, usually occurs at discrete luminal sites; thus, only small numbers of endothelial cells can be recruited to initiate anti-inflammatory responses. However, we, and others, have demonstrated that locally generated EDH spreads to endothelial cells and smooth muscle cells throughout a vessel to cause remote vasodilatation. In this article, we propose that, in addition to a widespread inhibitory signalling mechanism, EDH produced by the endothelium also initiates remote anti-inflammatory actions that prevent large blood vessels developing atherosclerosis.
Selemidis
Stavros
S
Dept of Pharmacology, The University of Melbourne, Victoria 3010, Australia.
Cocks
Thomas M
TM
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D001792:Blood Platelets / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology; D017382:Reactive Oxygen Species
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002118:Calcium