Phospholipid transfer protein in the placental endothelium is affected by gestational diabetes mellitus.

CONTEXT Gestational diabetes mellitus (GDM) causes alterations in fetal high-density lipoproteins (HDL). Because phospholipid transfer protein (PLTP) is important for HDL (re)assembly and is expressed in the human placenta, we hypothesized that circulating fetal and/or placental PLTP expression and activity are altered in GDM. DESIGN PLTP levels and activity were determined in maternal and fetal sera from GDM and controls. Placental PLTP was immunolocalized, and its expression was measured in placental tissue. PLTP regulation by glucose/insulin was studied in human endothelial cells isolated from placental vessels (HPEC). RESULTS Placental Pltp expression was up-regulated in GDM (1.8-fold, P < 0.05). PLTP protein (5-fold, P < 0.01) and activity (1.4- to 2.5-fold) were higher in fetal than in maternal serum. The placental endothelium was identified as a major PLTP location. Insulin treatment of HPEC significantly increased secreted PLTP levels and activity. In GDM, fetal cholesterol, HDL-triglycerides and phospholipids were elevated compared with controls. Fetal PLTP activity was higher than maternal but unaltered in GDM. CONCLUSION HPEC contribute to the release of active PLTP into the fetal circulation. Pltp expression is increased in GDM with hyperglycemia and/or hyperinsulinemia contributing. High PLTP activity in fetal serum may enhance conversion of HDL into cholesterol-accepting particles, thereby increasing maternal-fetal cholesterol transfer.

[1]  M. V. van Poppel,et al.  Dysregulation of Placental Endothelial Lipase in Obese Women With Gestational Diabetes Mellitus , 2011, Diabetes.

[2]  E. Herrera,et al.  Disturbances in lipid metabolism in diabetic pregnancy - Are these the cause of the problem? , 2010, Best practice & research. Clinical endocrinology & metabolism.

[3]  L. Leach,et al.  Vascular dysfunction in the diabetic placenta: causes and consequences , 2009, Journal of anatomy.

[4]  M. Lappas,et al.  Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus. , 2009, European journal of endocrinology.

[5]  U. Lang,et al.  Human Endothelial Cells of the Placental Barrier Efficiently Deliver Cholesterol to the Fetal Circulation via ABCA1 and ABCG1 , 2009, Circulation research.

[6]  P. Catalano,et al.  Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort , 2009, Diabetologia.

[7]  E. Korgun,et al.  Human fetal placental endothelial cells have a mature arterial and a juvenile venous phenotype with adipogenic and osteogenic differentiation potential. , 2008, Differentiation; research in biological diversity.

[8]  G. Egeland,et al.  Oxysterol as a marker of atherogenic dyslipidemia in adolescence. , 2008, The Journal of clinical endocrinology and metabolism.

[9]  M. Jauhiainen,et al.  Cholesterol efflux from macrophage foam cells is enhanced by active phospholipid transfer protein through generation of two types of acceptor particles. , 2007, Biochemistry.

[10]  S. Hauguel-de Mouzon,et al.  The Human Placenta in Gestational Diabetes Mellitus , 2007, Diabetes Care.

[11]  O. Monte,et al.  Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus , 2007, Diabetes/metabolism research and reviews.

[12]  M. Jauhiainen,et al.  Determination of human plasma phospholipid transfer protein mass and activity. , 2005, Methods.

[13]  A. Groen,et al.  Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment , 2005, Diabetologia.

[14]  D. Mangelsdorf,et al.  Placental expression of the nuclear receptors for oxysterols LXRα and LXRβ during mouse and human development , 2005 .

[15]  G. Desoye,et al.  Insulin binding to trophoblast plasma membranes and placental glycogen content in well-controlled gestational diabetic women treated with diet or insulin, in well-controlled overt diabetic patients and in healthy control subjects , 2004, Diabetologia.

[16]  A. Van der Laarse,et al.  Decreased PLTP mass but elevated PLTP activity linked to insulin resistance in HTG: effects of bezafibrate therapy. , 2003, Journal of lipid research.

[17]  A. Vaughan,et al.  Phospholipid transfer protein interacts with and stabilizes ABCA 1 and enhances cholesterol efflux from cells * , 2003 .

[18]  P. Eacho,et al.  Phospholipid Transfer Protein Is Regulated by Liver X Receptors in Vivo * , 2002, The Journal of Biological Chemistry.

[19]  C. Napoli,et al.  The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol‐lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  T. Oka,et al.  Isolation and Partial Characterization of the Inactive and Active Forms of Human Plasma Phospholipid Transfer Protein (PLTP)* , 2002, The Journal of Biological Chemistry.

[21]  Kunihiko Kobayashi,et al.  Unique character and metabolism of high density lipoprotein (HDL) in fetus. , 2002, Atherosclerosis.

[22]  R. Kirchmair,et al.  Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2 , 2001, International Journal of Obesity.

[23]  J. Albers,et al.  Glucose regulates the transcription of human genes relevant to HDL metabolism: responsive elements for peroxisome proliferator-activated receptor are involved in the regulation of phospholipid transfer protein. , 2001, Diabetes.

[24]  M. Jauhiainen,et al.  The Mechanism of the Remodeling of High Density Lipoproteins by Phospholipid Transfer Protein* , 2001, The Journal of Biological Chemistry.

[25]  M. Jauhiainen,et al.  Phospholipid transfer is a prerequisite for PLTP-mediated HDL conversion. , 2000, Biochemistry.

[26]  M. Bouchenak,et al.  Maternal and fetal serum lipid and lipoprotein concentrations and compositions in type 1 diabetic pregnancy: relationship with maternal glycemic control. , 2000, The Journal of laboratory and clinical medicine.

[27]  M. Nagano,et al.  Measurement of human plasma phospholipid transfer protein by sandwich ELISA. , 2000, Clinical chemistry.

[28]  B. Loukidi,et al.  Changes in serum lipid and lipoprotein concentrations and compositions at birth and after 1 month of life in macrosomic infants of insulin-dependent diabetic mothers , 1999, European Journal of Pediatrics.

[29]  J. Albers,et al.  Phospholipid transfer protein enhances removal of cellular cholesterol and phospholipids by high-density lipoprotein apolipoproteins. , 1999, Biochimica et biophysica acta.

[30]  P. Gambert,et al.  Plasma phospholipid transfer protein prevents vascular endothelium dysfunction by delivering α‐tocopherol to endothelial cells , 1999 .

[31]  J. Albers,et al.  Functional expression of human and mouse plasma phospholipid transfer protein: effect of recombinant and plasma PLTP on HDL subspecies. , 1995, Biochimica et biophysica acta.

[32]  Terri L. Gilbert,et al.  Complete cDNA encoding human phospholipid transfer protein from human endothelial cells. , 1994, The Journal of biological chemistry.

[33]  B. Föger,et al.  High density lipoproteins with differing apolipoproteins: relationships to postprandial lipemia, cholesteryl ester transfer protein, and activities of lipoprotein lipase, hepatic lipase, and lecithin: cholesterol acyltransferase. , 1994, Journal of lipid research.

[34]  C. Jones,et al.  Insulin and glucose do not affect the glycogen content in isolated and cultured trophoblast cells of human term placenta. , 1991, The Journal of clinical endocrinology and metabolism.

[35]  E. Gong,et al.  Apolipoprotein-specific populations in high density lipoproteins of human cord blood. , 1991, Biochimica et biophysica acta.

[36]  A. Tall,et al.  Plasma phospholipid transfer protein enhances transfer and exchange of phospholipids between very low density lipoproteins and high density lipoproteins during lipolysis. , 1985, Journal of lipid research.

[37]  C. Blum,et al.  Umbilical Cord Blood Lipoproteins: Isolation and Characterization of High Density Lipoproteins , 1983, Arteriosclerosis.

[38]  A. Cameron,et al.  THE DIABETIC PREGNANCY. A STUDY OF SERUM LIPIDS IN MATERNAL AND UMBILICAL CORD BLOOD AND OF THE UTERINE AND PLACENTAL VASCULATURE. , 1965, Archives of disease in childhood.