Dysregulation of placental endothelial lipase and lipoprotein lipase in intrauterine growth-restricted pregnancies.

CONTEXT Fetal supply of maternally derived fatty acids requires lipase-mediated hydrolysis of lipoprotein-borne triglycerides and phospholipids at the placental surface. OBJECTIVE The objective of the study was to test the hypothesis that members of the triglyceride lipase gene (TLG) family are expressed in the human placenta at the maternoplacental (syncytiotrophoblast) and fetoplacental (endothelial cells) interface and that their expression is altered in pregnancy pathologies. DESIGN AND SETTING Expression of TLG family members in primary placental cells (trophoblast and endothelial cells) and tissues of first-trimester and term human placenta was analyzed by microarrays, RT-PCR, Western blotting, and immunohistochemistry. Their expression was compared between normal pregnancies and those complicated with intrauterine growth restriction (IUGR). PARTICIPANTS Participants included women with uncomplicated pregnancies and pregnancies complicated by IUGR. RESULTS Endothelial lipase (EL) and lipoprotein lipase (LPL) were the only lipases among the TLG family expressed in key cells of the human placenta. In first trimester, EL and LPL were expressed in trophoblasts. At term, EL was detected in trophoblasts and endothelial cells, whereas LPL was absent in these cells. Both lipases were found at placental blood vessels, EL in vascular endothelial cells and LPL in the surrounding smooth muscle cells. In total placental tissue EL expression prevails in first trimester and at term. Compared with normal placentas, EL mRNA was decreased (30%; P < 0.02), whereas LPL mRNA expression was increased (2.4-fold; P < 0.015) in IUGR. CONCLUSION EL is the predominant TLG family member in the human placenta present at both interfaces. EL and LPL are dysregulated in IUGR.

[1]  I. Cetin,et al.  Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition. , 2007, American journal of physiology. Endocrinology and metabolism.

[2]  P. Damm,et al.  Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression Published, JLR Papers in Press, August 29, 2006. , 2006, Journal of Lipid Research.

[3]  I. Cetin,et al.  Placental LPL Gene Expression Is Increased in Severe Intrauterine Growth-Restricted Pregnancies , 2006, Pediatric Research.

[4]  N. Seidah,et al.  Proprotein Covertases Are Responsible for Proteolysis and Inactivation of Endothelial Lipase* , 2005, Journal of Biological Chemistry.

[5]  R. Zechner,et al.  Endothelial and lipoprotein lipases in human and mouse placenta Published, JLR Papers in Press, September 8, 2005. DOI 10.1194/jlr.M500277-JLR200 , 2005, Journal of Lipid Research.

[6]  G. Rechberger,et al.  Endothelial lipase releases saturated and unsaturated fatty acids of high density lipoprotein phosphatidylcholine Published, JLR Papers in Press, April 16, 2005. DOI 10.1194/jlr.M500054-JLR200 , 2005, Journal of Lipid Research.

[7]  M. Gauster,et al.  Endothelial lipase is inactivated upon cleavage by the members of the proprotein convertase family Published, JLR Papers in Press, February 1, 2005. DOI 10.1194/jlr.M400500-JLR200 , 2005, Journal of Lipid Research.

[8]  P. Haggarty.  Effect of placental function on fatty acid requirements during pregnancy , 2004, European Journal of Clinical Nutrition.

[9]  T. Powell,et al.  Triglyceride hydrolase activities and expression of fatty acid binding proteins in the human placenta in pregnancies complicated by intrauterine growth restriction and diabetes. , 2004, The Journal of clinical endocrinology and metabolism.

[10]  D. Rader,et al.  Endogenously Produced Endothelial Lipase Enhances Binding and Cellular Processing of Plasma Lipoproteins via Heparan Sulfate Proteoglycan-mediated Pathway* , 2003, Journal of Biological Chemistry.

[11]  G. Desoye,et al.  Heterogeneity of microvascular endothelial cells isolated from human term placenta and macrovascular umbilical vein endothelial cells. , 2003, European journal of cell biology.

[12]  R. Zechner,et al.  Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity. , 2002, The Biochemical journal.

[13]  R. Zechner,et al.  Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism , 2002, Current opinion in lipidology.

[14]  D. Rader,et al.  Lipase H, a new member of the triglyceride lipase family synthesized by the intestine. , 2002, Genomics.

[15]  L. Martinez,et al.  Hepatic lipase: structure/function relationship, synthesis, and regulation. , 2002, Journal of lipid research.

[16]  D. Rader,et al.  Characterization of the lipolytic activity of endothelial lipase. , 2002, Journal of lipid research.

[17]  H. Arai,et al.  Structure and function of phosphatidylserine-specific phospholipase A1. , 2002, Biochimica et biophysica acta.

[18]  J. Hobbins,et al.  Intrauterine growth restriction (IUGR): biometric and Doppler assessment , 2002, Prenatal diagnosis.

[19]  D. Strickland,et al.  Transcytosis of Lipoprotein Lipase across Cultured Endothelial Cells Requires Both Heparan Sulfate Proteoglycans and the Very Low Density Lipoprotein Receptor* , 2001, The Journal of Biological Chemistry.

[20]  M. Lowe,et al.  Properties and function of pancreatic lipase related protein 2. , 2000, Biochimie.

[21]  G. Desoye,et al.  Antibody reaction patterns in first trimester placenta: implications for trophoblast isolation and purity screening. , 2000, Placenta.

[22]  Sungshin Y. Choi,et al.  Cloning of a Unique Lipase from Endothelial Cells Extends the Lipase Gene Family* , 1999, The Journal of Biological Chemistry.

[23]  D. Rader,et al.  A novel endothelial-derived lipase that modulates HDL metabolism , 1999, Nature Genetics.

[24]  G. Desoye,et al.  Paracrine regulation of distinct trophoblast functions in vitro by placental macrophages , 1999, Cell and Tissue Research.

[25]  P. Barboni,et al.  Pancreatic lipase-related protein 1 (PLRP1) is present in the pancreatic juice of several species. , 1998, Biochimica et biophysica acta.

[26]  M. Amar,et al.  The role of hepatic lipase in lipoprotein metabolism and atherosclerosis , 1998 .

[27]  D. Schwartz,et al.  Culture of first-trimester and full-term human chorionic villus explants: role of human chorionic gonadotropin and human placental lactogen as a viability index. , 1995, Early pregnancy : biology and medicine : the official journal of the Society for the Investigation of Early Pregnancy.

[28]  T. Olivecrona,et al.  Triglyceride lpases and atherosclerosis , 1995 .

[29]  A. Kosaki,et al.  The B Isoform of the Insulin Receptor Signals More Efficiently Than the A Isoform in HepG2 Cells (*) , 1995, The Journal of Biological Chemistry.

[30]  J. Taylor,et al.  Enhanced binding and uptake of remnant lipoproteins by hepatic lipase-secreting hepatoma cells in culture. , 1994, The Journal of biological chemistry.

[31]  L. Fedele,et al.  [Standards of birth weight in Italy]. , 1991, Annali di ostetricia, ginecologia, medicina perinatale.

[32]  F. Winkler,et al.  Structure of human pancreatic lipase , 1990, Nature.

[33]  A. Bensadoun,et al.  Secretion and degradation of lipoprotein lipase in cultured adipocytes. Binding of lipoprotein lipase to membrane heparan sulfate proteoglycans is necessary for degradation. , 1989, The Journal of biological chemistry.

[34]  B. Lewis,et al.  Evaluation of the roles of lipoprotein lipase and hepatic lipase in lipoprotein metabolism: in vivo and in vitro studies in man , 1980, European journal of clinical investigation.

[35]  M. Bilban,et al.  Insulin control of placental gene expression shifts from mother to foetus over the course of pregnancy , 2005, Diabetologia.