Highlights
- •Lipid Phosphate Phosphatase 3 (LPP3) is an enzyme encoded by the PLPP3 gene.
- •LPP3 catalyses the dephosphorylation of extracellular and intracellular lipids.
- •The lack of LPP3 leads to profound alterations in cardiovascular development.
- •Polymorphisms in the PLPP3 gene are associated with CAD susceptibility.
- •Hepatic deficiency of LPP3 in mice worsens atherosclerosis development.
Abstract
LPP3 is an integral membrane protein belonging to a family of enzymes (LPPs) that
display broad substrate specificity and catalyse dephosphorylation of several lipid
substrates, including lysophosphatidic acid and sphingosine-1-phosphate.
In mammals, the LPP family consists of three enzymes named LPP1, LPP2 and LPP3, which
are encoded by three independent genes, PLPP1, PLPP2 and PLPP3, respectively (formerly known as PPAP2A, PPAP2C, PPAP2B). These three enzymes, in vitro, do not seem to differ for catalytic activities and substrate preferences. However,
in vivo targeted inactivation of the individual genes has indicated that the enzymes do not
have overlapping functions and that LPP3, specifically, plays a crucial role in vascular
development.
In 2011, two genome-wide association studies have identified PLPP3 as a novel locus associated with coronary artery disease susceptibility. Shortly after these reports,
tissue specific inactivation of PLPP3 in mice highlighted a specific role for LPP3 in vascular pathophysiology and, more
recently, in atherosclerosis development.
This review is aimed at providing an updated overview on the function of LPP3 in embryonic
cardiovascular development and on the experimental and clinical evidences relating
this enzyme to vascular cell functions and cardiovascular disease.
Keywords
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Article Info
Publication History
Published online: February 23, 2018
Accepted:
February 20,
2018
Received in revised form:
February 2,
2018
Received:
December 22,
2017
Identification
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© 2018 Elsevier B.V. All rights reserved.
