Abstract
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.
Keywords:
atherosclerosis; lipid phosphate phosphatase; lysophosphatidic acid.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adipose Tissue / enzymology
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Animals
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Apolipoproteins E / deficiency
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Atherosclerosis / genetics
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Atherosclerosis / metabolism*
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Coronary Artery Disease / epidemiology
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Coronary Artery Disease / genetics
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Coronary Artery Disease / prevention & control
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Genetic Predisposition to Disease
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Humans
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Lysophospholipids / metabolism
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Lysophospholipids / physiology*
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Mice
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Mice, Knockout
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Phosphatidate Phosphatase / deficiency
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Phosphatidate Phosphatase / genetics
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Phosphatidate Phosphatase / physiology*
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Phosphoric Diester Hydrolases / physiology*
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Plaque, Atherosclerotic / metabolism
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Risk
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Sphingosine / analogs & derivatives
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Sphingosine / metabolism
Substances
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Apolipoproteins E
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Lysophospholipids
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sphingosine 1-phosphate
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lipid phosphate phosphatase
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PLPP3 protein, human
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Phosphatidate Phosphatase
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Plpp3 protein, mouse
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Phosphoric Diester Hydrolases
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alkylglycerophosphoethanolamine phosphodiesterase
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Sphingosine
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lysophosphatidic acid