Regulation Of Vascular Cell Function By Lipid Phosphate Phosphatase 3 | 3113
Journal of Clinical & Experimental Pathology
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Meta-analysis of data from a series of genome-wide association studies (GWAS) revealed a striking association between the
PPAP2B loci and coronary artery disease. The PPAP2B gene encodes for the lipid phosphate phosphatase 3 (LPP3) integral
membrane enzyme, that dephosphorylates lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P) and related bioactive
lipids. While emerging evidence suggests a role for both LPA and S1P in experimental models of atherosclerosis, essentially
nothing is understood about the pathophysiologic role of LPP3, largely due to the fact that genetic inactivation results embryonic
lethality. We report that constitutive inactivation of LPP3 in vascular cells accomplished by breeding mice with floxed Ppap2b
to mice expressing Cre recombinase under control of the Tie1 or SM22 promoter results in dysregulation of LPP3-dependent
vascular endothelial cell and smooth muscle cell (SMC) functions which likely underlies the developmental phenotype observed
in Ppap2b-null embryos. Using an estrogen inducible Cre transgene under control of the Tie1 promoter, we have inactivated
Ppap2b expression in endothelial cells in adult mice. The absence of vascular endothelial LPP3 results in an increase in basal
vascular permeability, as assessed by Evans blue dye extravasation in lung tissue. Our observations with respect to SMC suggest
that LPP3 serves as an intrinsic negative regulator of SMC phenotypic modulation and inflammation after vascular injury, in part
by regulating LPA signaling and act as an important endogenous mediator of development of intimal hyperplasia.
Manikandan Panchatcharam has completed his Ph.D at the age of 31 years from University of Madras and postdoctoral studies from University of North Carolina at Chapel Hill, Carolina Cardiovascular Biology Center. He is an assistant professor at University of Kentucky. He has published more than 23 papers in reputed journals and serving as an editorial board member of repute.
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