Endothelin-1 signalling in vascular smooth muscle: pathways controlling cellular functions associated with atherosclerosis.
Atherosclerosis is the primary ischaemic vascular condition underlying a majority of cardiovascular disease related deaths. Endothelin-1 is a vasoactive peptide agent upregulated in atherosclerosis and in conjunction with its G protein-coupled receptors exerts diverse actions on all cells of the vasculature in particular vascular smooth muscle cells (VSMC). The effects of endothelin-1 include cell proliferation, migration and contraction, and the induction of extracellular matrix components and growth factors. VSMC as the major component of the neointima in atherosclerotic plaques accordingly play a key role in atherogenesis. In this review we examine classic and novel signalling pathways activated by endothelin-1 in VSMC (including phospholipase C, adenylate cyclase, Rho kinase, transactivation of receptor tyrosine kinases, mitogen activated protein kinase cascades and beta-arrestin) and their likely impact on the development and progression of atherosclerosis.
Ivey
Melanie E
ME
Cell Biology of Diabetes Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia.
Osman
Narin
N
Little
Peter J
PJ
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D019332:Endothelin-1 / Q000096:biosynthesis*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D015398:Signal Transduction; D015533:Transcriptional Activation
D019332:Endothelin-1; D010455:Peptides