Arguing the case for the autotaxin-lysophosphatidic acid-lipid phosphate phosphatase 3-signaling nexus in the development and complications of atherosclerosis.
The structurally simple glycero- and sphingo-phospholipids, lysophosphatidic acid (LPA) and sphingosine-1-phosphate, serve as important receptor-active mediators that influence blood and vascular cell function and are positioned to influence the events that contribute to the progression and complications of atherosclerosis. Growing evidence from preclinical animal models has implicated LPA, LPA receptors, and key enzymes involved in LPA metabolism in pathophysiologic events that may underlie atherosclerotic vascular disease. These observations are supported by genetic analysis in humans implicating a lipid phosphate phosphatase as a novel risk factor for coronary artery disease. In this review, we summarize current understanding of LPA production, metabolism, and signaling as may be relevant for atherosclerotic and other vascular disease.
From the Veterans Affairs Medical Center, Cardiovascular Medicine Service, Lexington, KY (S.S.S., A.J.M.); and Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY (S.S.S., P.M., F.Y., J.A.B., A.J.M.).
Susan S
SS
Smyth
Paul
P
Mueller
Fanmuyi
F
Yang
J Anthony
JA
Brandon
Andrew J
AJ
Morris
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D020022:Genetic Predisposition to Disease; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010711:Phosphatidate Phosphatase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D012306:Risk; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D000099189:Lysophospholipase D
D001057:Apolipoproteins E; D008246:Lysophospholipids; D010711:Phosphatidate Phosphatase; D010727:Phosphoric Diester Hydrolases; D013110:Sphingosine; D000099189:Lysophospholipase D; C060506:sphingosine 1-phosphate; C112948:lipid phosphate phosphatase; C521833:PLPP3 protein, human; C479566:Plpp3 protein, mouse; C032881:lysophosphatidic acid
atherosclerosis; lipid phosphate phosphatase; lysophosphatidic acid