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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 3 1162-1166
Copyright © 2003 by The Endocrine Society

Triglyceride-Rich Lipoproteins Are Associated with Hypertension in Preeclampsia

Karl Winkler, Birgit Wetzka, Michael M. Hoffmann, Isolde Friedrich, Martina Kinner, Manfred W. Baumstark, Hans-Peter Zahradnik, Heinrich Wieland and Winfried März

Departments of Clinical Chemistry (K.W., M.M.H., I.F., H.W.), Obstetrics and Gynecology (B.W., M.K., H.-P.Z.), and Sports Medicine (M.W.B.), University of Freiburg, Germany; and Clinical Institute of Medical and Chemical Laboratory Diagnostics (W.M.), University of Graz, Graz, Austria

Address all correspondence and requests for reprints to: Karl Winkler, M.D., Department of Clinical Chemistry, School of Medicine, Albert Ludwigs-University, Hugstetter Strasse 55, D-79106 Freiburg, Germany. E-mail: kwinkler{at}ukl.uni-freiburg.de.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
Disorders of the lipoprotein metabolism are a major cause of endothelial dysfunction that may result in hypertension and proteinuria, clinical hallmarks of preeclampsia (PE). Lipoproteins and low-density lipoprotein (LDL) subfractions were investigated in 15 women with severe PE and compared with 23 women with a normal course of pregnancy. Compared with normal pregnancy, in PE apolipoprotein (apo)B in very low-density lipoprotein was increased by 76% (P = 0.008), and the triglyceride content of intermediate dense lipoproteins (IDL) was increased by 51% (P < 0.001); cholesterol and apoB in LDL were decreased by 26% (P = 0.005) and 23% (P = 0.016), respectively. Although not significant, the LDL profile was dominated by the most buoyant LDL-1. ApoB in the most dense LDL (dLDL), namely LDL-5 and LDL-6, was significantly decreased by 49% (P < 0.001) and 55% (P < 0.001), respectively. Diastolic blood pressure was positively correlated with the triglyceride content of IDL (r = 6.31; P < 0.001 and r = 0.352; P = 0.033 by partial correlation controlling for the presence or absence of PE) and negatively correlated with the concentration of apoB in dLDL (r = -0.500; P = 0.002). In addition, IDL triglycerides correlated negatively with infant birth weight percentile (r = -0.373; P = 0.027) and positively with proteinuria (r = 0.430; P = 0.014). Low birth weight was associated with high IDL triglycerides and low rather than high concentrations of dLDL. Triglyceride-rich remnants are known to cause endothelial dysfunction. Because the triglyceride content of IDL was positively correlated with elevated blood pressure and proteinuria, triglyceride-rich remnant lipoproteins might contribute to the pathophysiology of PE.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
PREECLAMPSIA (PE) IS the leading cause of maternal and neonatal mortality (1). In PE there is an increased vascular sensitivity to pressors (2), and the coagulation and fibrinolytic cascades are highly activated (3). Most of these symptoms including proteinuria may be explained by endothelial dysfunction (4). Sera of preeclamptic women contain unknown components that change the metabolic and functional properties of cultured endothelial cells (5). Endothelial dysfunction may result from disorders of lipoprotein metabolism (6), and it was suggested that small, dense low-density lipoprotein (LDL) may contribute to endothelial dysfunction in PE (7, 8).

However, specifically triglyceride-rich lipoproteins may also trigger endothelial dysfunction (9) and atherothrombosis (10). Using some of the same individuals as in this study, we recently observed a significant negative correlation between maternal platelet counts and serum triglyceride (TG) levels (11).

Given the accumulation of buoyant, TG-rich lipoproteins in late pregnancy (12) and the potentially detrimental effects of these particles on the endothelium, we set out with the hypothesis that high levels of buoyant apolipoprotein (apo)B containing particles play a key role in the development of the clinical symptoms of PE. To substantiate this hypothesis, we examined lipoproteins and lipoprotein subfractions in normal pregnancy and PE.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Patients and study protocol

Fifteen preeclamptic women were studied. Eleven women were delivered by primary cesarean section (CS) for fetal and/or maternal reasons. In three women labor was induced by prostaglandin E2. However, the patients still needed to be delivered by CS because of fetal distress in the early stage of labor. One woman had premature rupture of membranes in the 35th week and was then also delivered by CS. Blood was always collected before the onset of labor. Parity of the preeclamptic women was eight times one, five times two, and two times three pregnancies, including the present one. PE was defined by hypertension (blood pressure > 140 mm Hg systolic and 90 mm Hg diastolic) on repeated readings and proteinuria of 2+ or greater on dipstick testing according to the International Society for the Study of Hypertension in Pregnancy (13). In addition, 23 women with a regular course of pregnancy were investigated as previously described (12). Of these, 19 women delivered spontaneously, three women had a primary, and one a secondary CS. Parity of the women with normal pregnancy was 16 times one, two times two, two times three, two times four, and one times five pregnancies, including the present one. Immediately after venipuncture, blood samples were sent to the Department of Clinical Chemistry at the University of Freiburg, and blood cells were removed. Before analysis plasma was stored at 5 C for a maximum period of 3 d. There was no subject homozygous for apoE2 in either of the two groups. None of the subjects received medication known to influence the lipid metabolism. This study was approved by the Ethics Review Committee of the University of Freiburg. Informed consent was obtained from each subject, and all procedures were in accordance with the Helsinki Declaration of 1975, revised in 1983.

Lipoprotein separation

Lipoproteins were isolated by sequential preparative ultracentrifugation using the following densities: density less than 1.006 kg/liter for very low-density lipoprotein (VLDL), 1.006 less than density less than 1.019 for intermediate dense lipoproteins (IDL), 1.019 less than density less than 1.063 kg/liter for LDL, and 1.063 less than density less than 1.21 for high-density lipoproteins (HDL). LDL subfractions were separated according to Baumstark et al. (14). Total LDLs were fractionated into six density classes: LDL-1, 1.019–1.031 kg/liter; LDL-2, 1.031–1.034 kg/liter; LDL-3, 1.034–1.037 kg/liter; LDL-4, 1.037–1.040 kg/liter; LDL-5, 1.040–1.044 kg/liter; LDL-6, 1.044–1.063 kg/liter. The interassay coefficient of variance of apoB for the six LDL subfractions was 5% and below (12).

Lipoprotein chemistry

Cholesterol (CH) and TGs were determined enzymatically using the CHOD-PAP and the GPO-PAP method (Roche Diagnostics, Mannheim, Germany), respectively. Concentrations of apoproteins were determined by turbidimetry on a 30R analyzer (Wako Chemicals, Osaka, Japan) using specific polyclonal antisera (Rolf Greiner Biochemica, Flacht, Germany) for the respective antigen.

Statistical analysis

Differences of clinical characteristics and lipoprotein parameters of preeclamptic women and the third trimester of normal pregnancy (controls) were tested for significance using the nonparametric Mann-Whitney U test. Bivariate correlations were analyzed by Pearson’s correlation coefficients. In addition, continuous variables were studied by bivariate partial correlation analysis controlling for the absence (coded as 1) or the presence (coded as 2) of PE. Significance was assumed if the P value was less than 0.05.


   Results
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 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
Women with an uncomplicated course of pregnancy were investigated during routine check-ups in the 12th, 22nd, and the 34th week of gestation (12). The median gestational age at blood sampling in preeclamptic women was 34.4 wk (range, 27–39). This matches the gestational age (median, 32.6; range, 26–40 wk) of the control subjects (Table 1Go). Diastolic blood pressure was elevated above 90 mm Hg, proteinuria was between 2+ and 3+ on dipstick testing, and total protein and platelet counts were decreased in preeclamptic women (Table 1Go). There was no difference between the normal pregnant and preeclamptic group with regard to age and body mass index before pregnancy. The average birth weight percentile of the babies of preeclamptic women was significantly lower, compared with babies of women with a normal course of pregnancy (Table 1Go).


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  		Table 1. Clinical characteristics (median and interquartile range)

 
In PE, TGs, apoC-II and apoE levels were significantly elevated, whereas CH, apoA-I, apoA-II, apoB, and apoC-III did not differ substantially (Table 2Go), compared with the third trimester of normal gestation. In the VLDL fraction, CH, TGs, and apoB levels were significantly increased, whereas LDL CH and LDL apoB were significantly decreased (Table 3Go). Although not significant, there was a preponderance of LDL-1, the most buoyant LDL fraction, whereas the dense LDL (dLDL) fractions LDL-5 and LDL-6 were significantly reduced, compared with normal pregnancy of the same gestational age (Fig. 1Go). IDL as well as LDL and HDL were significantly enriched with TGs, as evidenced by the ratio of TGs to apoB and apoA-I, respectively (Table 3Go). When both groups of women, controls and preeclamptic women, were considered together, diastolic blood pressure was negatively correlated with the concentration of apoB in dLDL and the TG content of IDL. In addition, IDL TGs correlated negatively with infant birth weight percentile and positively with proteinuria (Fig. 2Go). The association of IDL TGs with diastolic blood pressure was robust if we performed partial correlation analysis controlling for the case-control status, i.e. normal or PE (Fig. 2BGo).


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  		Table 2. Lipids and apolipoproteins (median and interquartile range)

 

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  		Table 3. Lipoprotein composition (median and interquartile range)

 


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  		Figure 1. Concentration of apoB in VLDL, IDL, and LDL subfractions. V, I, L-1 through L-6, VLDL, IDL, and LDL-1 through LDL-6, respectively. Controls ({circ}) (n = 23); PE (•) (n = 15). Mann-Whitney U test: **, P < 0.01; ***, P < 0.001. Error bars represent SE of the mean (SEM).

 


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  		Figure 2. Correlation of apoB in dLDL (A) and TG content (TG/apoB) of IDL (B) with diastolic blood pressure (DBP) and TG content (TG/apoB) of IDL with infant birth weight (C) and proteinuria (D). Controls ({circ}) (n = 23); PE (•) (n = 15). Apo B in dLDL refers to the concentration of apoB in LDL-5 plus LDL-6. Bivariate correlations were analyzed using Pearson’s correlation coefficients. No regression lines are shown in cases in which correlation coefficients were no longer statistically significantly different from zero after adjusting for the case-control status (presence or absence of PE). The association of IDL TGs and diastolic blood pressure (B) was robust to adjustment for the case-control status by partial regression analysis (partial correlation coefficient framed by a double line).

 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
Plasma lipids in normal pregnancy are at atherogenic levels, even more so in PE. Compared with normal pregnancy of the same gestational age, the preeclamptic women described here showed significantly elevated levels of TG-rich VLDL particles (Fig. 1Go). This is in line with numerous earlier reports.

In PE, LDL CH and LDL apoB was low, compared with normal pregnancy (Table 3Go), which is in agreement with studies by Sattar et al. (7) and Belo et al. (15), who found a reduction of LDL CH in preeclamptic women, although this was not statistically significant.

However, we found no predominance of dLDL in PE as claimed by two research groups. Sattar et al. (7) used nonequilibrium density-gradient ultracentrifugation to separate LDL by flotation rate into three subfractions (LDL-I, LDL-II, and LDL-III) in eight preeclamptic women matched with eight controls. Seven of eight controls had low LDL-III and six of eight preeclamptic women showed elevated LDL-III (P = 0.024). Using nondenaturing PAGE, Hubel et al. (8) investigated the LDL peak particle diameter. They reported the LDL peak particle diameter to be decreased in 20 preeclamptic women, compared with 20 women with a normal course of pregnancy.

To the contrary, we found a dominance of buoyant LDL-1 and a statistically highly significant decrease of dLDL, namely LDL-5 and LDL-6 (Fig. 1Go). In line with our findings, Belo et al. (15) reported the relative proportions of LDL-III, the smallest LDL as determined by gradient PAGE, to be reduced in the third trimester of 51 preeclamptic women (LDL-III, 33.4% of total LDL), compared with the third trimester of 67 women with normal pregnancy (LDL-III, 36.9% of total LDL), although this reduction was not statistically significant.

The overt discrepancy between the data of Sattar and Hubel and ours may be due to the different methodologies used, as discussed previously (12): nondenaturing gradient gel electrophoresis separates LDL by virtue of size and provides an estimate of the particle diameter of the major LDL peak (16). The density gradient ultracentrifugation used by Sattar et al. does not reach isopycnic equilibrium (17) and, therefore, separates LDL by virtue of flotation rate. The flotation rate depends on both particle buoyancy and the size of the particle. It thus appears that the studies conducted earlier examined the LDL subfraction profile with methods depending on particle size. In contrast, the method used in this study strictly separates LDL subfractions by virtue of their density (14), revealing a highly significant (Fig. 1Go) decrease of dense LDL in preeclamptic women.

In late gestation, high amounts of TGs are found not only in VLDL but also in IDL, LDL, and HDL (12, 18). A mechanism specific to pregnancy seems to be responsible for this phenomenon: the removal of lipoprotein TGs is reduced because os decreasing activities of lipoprotein lipase (LPL) and hepatic lipase (HL), the effect being more striking for HL than for LPL (19, 20).

In contrast to normal pregnancy, Sattar et al. (7) reported that HL activity is increased in PE. Endresen et al. (21) also found increased lipolytic activity and increased fatty acid levels in sera from preeclamptic women. However, the increased lipolytic activity encountered by Endresen et al. was due to a lysophospholipase not hydrolyzing TGs or diglycerides (22). This activity might be different from HL and LPL, which hydrolyze TGs in circulating lipoproteins (23). Therefore, the findings by Endresen et al. are not inconsistent with the assumption of decreased lipolysis of lipoproteins in PE. A conclusive explanation, however, for the discrepancy between the findings by Sattar et al. and the current ones is not apparent so far.

Although on a higher level, the lipoprotein metabolism in preeclampsia appears to be similar to that in normal pregnancy, with the important additional feature of the depletion of dLDL particles (Fig. 1Go). This suggests that there might be an even more profound decrease in the hydrolysis of TGs, compared with normal gestation, resulting in an impaired generation of LDL particles from TG-rich lipoproteins.

Insufficient lipolysis of TG-rich lipoproteins leads to the accumulation of remnant lipoproteins, which are otherwise quickly removed for the circulation, with an increased TG content and prolonged residence time.

The conversion of IDL to LDL is mainly mediated by HL (24, 25). Patients suffering from acquired (26) or familial (27, 28) HL deficiency accumulate large, buoyant LDLs that are enriched in TGs and depleted in CH, the same being true for HDLs (27, 29). Similar alterations in lipoprotein composition were observed in our patients with PE (Table 3Go). In addition, the accumulation of the most buoyant LDL fraction together with low levels of dLDL particles (Fig. 1Go) has recently been described as a hallmark of familial HL deficiency (28). The changes in lipoprotein metabolism observed in PE thus closely resemble those seen in HL deficiency.

In the late phase of pregnancy, estrogen enhances the production of VLDLs and decreases maternal lipolytic activity (19, 20). Together with the increased expression of the VLDL/apoE receptors in the placenta (30), this may result in a coordinated rerouting of TG-rich lipoproteins from the mother toward the fetoplacental unit to meet the nutritional demands of the growing fetus (12). However, in PE constrained fetal utilization of nutrients may result in chronic fetal distress and growth retardation. We hypothesized that the reduced maternal lipolysis and the hampered uptake of TG-rich lipoproteins by the fetoplacental unit lead to the accumulation of TG-rich remnant lipoproteins in the maternal circulation (Fig. 3Go). Although not robust to adjustment for the case-control status, i.e. normal pregnancy or PE, this is supported by the fact that there was a negative correlation of infant birth weight percentile and TG content of IDL particles (Fig. 2Go).



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  		Figure 3. Lipid metabolism in PE. In pregnancy, lipolysis of TG-rich lipoproteins is reduced because of decreased lipolytic activities of the mother (19 20 ), whereas placental VLDL receptors are up-regulated (30 ). This results in a rerouting of TG-rich lipoproteins to the fetoplacental unit (12 ). However, in PE, the vascularization of the fetoplacental unit may be impaired, resulting in yet-undefined compensatory mechanisms that may further increase synthesis of maternal TG levels (A). In addition, the decreased catabolism of TG-rich lipoproteins by reduced placental uptake (B) and the putative concomitant decrease of lipoprotein lipolysis (C) results in the accumulation of TG-rich remnant lipoproteins in the maternal circulation. Remnant lipoproteins may induce platelet activation and endothelial dysfunction, thus leading to the major clinical symptoms of PE.

 
Remnant accumulation may reflect not only insufficient uptake of these particles by the fetoplacental unit but may also be pivotal to the development of clinical symptoms of PE. Renal protein excretion and hypertension may both reflect endothelial dysfunction. Arbogast et al. (31) hypothesized that TG-rich lipoproteins from preeclamptic women damage the endothelium. Indeed, remnant lipoproteins are associated with impaired endothelial vasomotor function (9), and earlier studies reported that women with PE have an increased pressor response to angiotensin (2). In line with this, we observed an association of the accumulation of TGs in IDL particles and the depletion of dLDL particles with diastolic blood pressure and of IDL triglycerides with proteinuria (Fig. 2Go). This suggests that the alteration of the lipoprotein metabolism plays a key role in the development of the primary symptoms of PE.

To date, the only effective treatment of PE is the termination of pregnancy. However, a major problem consists in the immaturity of the fetus delivered preterm resulting in a high morbidity and mortality rate. Thus, our findings may be relevant for understanding the pathophysiology of PE and the future treatment by lipid modifying regimens of this life-threatening condition, for example, by drug therapy or lipoprotein apheresis.


   Acknowledgments
 
We are grateful to Ronald C. Reitz (Department of Biochemistry, University of Nevada, Reno, NV) for valuable discussion and Stephan Sorichter (Department of Internal Medicine, University of Freiburg, Freiburg, Germany) and Victor David Thiessen (St. Catharines, Ontario, Canada) for editing the manuscript. This study is dedicated to Johannes Wetzka, who was intimately involved in the generation of this work.


   Footnotes
 
Abbreviations: apo, Apolipoprotein; CH, cholesterol; CS, cesarean section; dLDL, dense low-density lipoprotein; HDL, high-density lipoprotein; HL, hepatic lipase; IDL, intermediate dense lipoprotein; LDL, low-density lipoprotein; LPL, lipoprotein lipase; PE, preeclampsia; TG, triglyceride; VLDL, very low-density lipoprotein.

Received July 24, 2002.

Accepted November 22, 2002.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Dunn PM 1995 Major ethical problems confronting perinatal care around the world. Int J Gynaecol Obstet 51:205–210[CrossRef][Medline]
  2. Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC 1973 A study of angiotensin II pressor response throughout primigravid pregnancy. J Clin Invest 52:2682–2689
  3. Graeff H, von Hugo R, Schrock R 1984 Recent aspects of hemostasis, hematology and hemorheology in preeclampsia-eclampsia. Eur J Obstet Gynecol Reprod Biol 17:91–102[CrossRef][Medline]
  4. Dekker GA, van Geijn HP 1996 Endothelial dysfunction in preeclampsia. Part I: Primary prevention. Therapeutic perspectives. J Perinat Med 24:99–117[Medline]
  5. Lorentzen B, Endresen MJ, Hovig T, Haug E, Henriksen T 1991 Sera from preeclamptic women increase the content of triglycerides and reduce the release of prostacyclin in cultured endothelial cells. Thromb Res 63:363–372[CrossRef][Medline]
  6. Zeiher AM, Drexler H, Wollschlager H, Just H 1991 Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 83:391–401[Abstract/Free Full Text]
  7. Sattar N, Bendomir A, Berry C, Shepherd J, Greer IA, Packard CJ 1997 Lipoprotein subfraction concentrations in preeclampsia: pathogenic parallels to atherosclerosis. Obstet Gynecol 89:403–408[CrossRef][Medline]
  8. Hubel CA, Lyall F, Weissfeld L, Gandley RE, Roberts JM 1998 Small low-density lipoproteins and vascular cell adhesion molecule-1 are increased in association with hyperlipidemia in preeclampsia. Metabolism 47:1281–1288[CrossRef][Medline]
  9. Kugiyama K, Doi H, Motoyama T, Soejima H, Misumi K, Kawano H, Nakagawa O, Yoshimura M, Ogawa H, Matsumura T, Sugiyama S, Nakano T, Nakajima K, Yasue H 1998 Association of remnant lipoprotein levels with impairment of endothelium-dependent vasomotor function in human coronary arteries. Circulation 97:2519–2526[Abstract/Free Full Text]
  10. Mochizuki M, Takada Y, Urano T, Nagai N, Nakano T, Nakajima K, Takada A 1996 The in vitro effects of chylomicron remnant and very low density lipoprotein remnant on platelet aggregation in blood obtained from healthy persons. Thromb Res 81:583–593[CrossRef][Medline]
  11. Wetzka B, Winkler K, Kinner M, Friedrich I, März W, Zahradnik HP 1999 Altered lipid metabolism in preeclampsia and HELLP syndrome: links to enhanced platelet reactivity and fetal growth. Semin Thromb Hemost 25:455–462[Medline]
  12. Winkler K, Wetzka B, Hoffmann MM, Friedrich I, Kinner M, Baumstark MW, Wieland H, März W 2000 Low density lipoprotein (LDL) subfractions during pregnancy: accumulation of buoyant LDL with advancing gestation. J Clin Endocrinol Metab 85:4543–4550[Abstract/Free Full Text]
  13. Davey DA, MacGillivray I 1988 The classification and definition of hypertensive disorders of pregnancy. Am J Obstet Gynecol 158:892–898[Medline]
  14. Baumstark MW, Kreutz W, Berg A, Frey I, Keul J 1990 Structure of human low-density lipoprotein subfractions, determined by X-ray small-angle scattering. Biochim Biophys Acta 1037:48–57[CrossRef][Medline]
  15. Belo L, Caslake M, Gaffney D, Santos-Silva A, Pereira-Leite L, Quintanilha A, Rebelo I 2002 Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies. Atherosclerosis 162:425–432[CrossRef][Medline]
  16. Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM 1988 Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 260:1917–1921[Abstract/Free Full Text]
  17. Griffin BA, Caslake MJ, Yip B, Tait GW, Packard CJ, Shepherd J 1990 Rapid isolation of low density lipoprotein (LDL) subfractions from plasma by gradient ultracentrifugation. Atherosclerosis 83:59–67[CrossRef][Medline]
  18. Montelongo A, Lasuncion MA, Pallardo LF, Herrera E 1992 Longitudinal study of plasma lipoproteins and hormones during pregnancy in normal and diabetic women. Diabetes 41:1651–1659[Abstract]
  19. Kinnunen PK, Unnerus HA, Ranta T, Ehnholm C, Nikkilä EA, Seppälä M 1980 Activities of postheparin plasma lipoprotein lipase and hepatic lipase during pregnancy and lactation. Eur J Clin Invest 10:469–474[Medline]
  20. Alvarez JJ, Montelongo A, Iglesias A, Lasuncion MA, Herrera E 1996 Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and postheparin lipases during gestation in women. J Lipid Res 37:299–308[Abstract]
  21. Endresen MJ, Lorentzen B, Henriksen T 1992 Increased lipolytic activity and high ratio of free fatty acids to albumin in sera from women with preeclampsia leads to triglyceride accumulation in cultured endothelial cells. Am J Obstet Gynecol 167:440–447[Medline]
  22. Endresen MJ, Lorentzen B, Henriksen T 1993 Increased lipolytic activity of sera from pre-eclamptic women due to the presence of a lysophospholipase. Scand J Clin Lab Invest 53:733–739[Medline]
  23. Dugi KA, Dichek HL, Santamarina-Fojo S 1995 Human hepatic and lipoprotein lipase: the loop covering the catalytic site mediates lipase substrate specificity. J Biol Chem 270:25396–25401[Abstract/Free Full Text]
  24. Jansen H, van Tol A, Hülsmann WC 1980 On the metabolic function of heparin-releasable liver lipase. Biochem Biophys Res Commun 92:53–59[CrossRef][Medline]
  25. Demant T, Carlson LA, Holmquist L, Karpe F, Nilsson-Ehle P, Packard CJ, Shepherd J 1988 Lipoprotein metabolism in hepatic lipase deficiency: studies on the turnover of apolipoprotein B and on the effect of hepatic lipase on high density lipoprotein. J Lipid Res 29:1603–1611[Abstract]
  26. Goldberg IJ, Mazlen RG, Rubenstein A, Gibson JC, Paterniti JRJ, Lindgren FT, Brown WV 1985 Plasma lipoprotein abnormalities associated with acquired hepatic triglyceride lipase deficiency. Metabolism 34:832–835[CrossRef][Medline]
  27. Knudsen P, Antikainen M, Ehnholm S, Uusi-Oukari M, Tenkanen H, Lahdenperä S, Kahri J, Tilly-Kiesi M, Bensadoun A, Taskinen MR, Ehnholm C 1996 A compound heterozygote for hepatic lipase gene mutation Leu334-> Phe and Thr383-> Met: correlation between hepatic lipase activity and phenotypic expression. J Lipid Res 37:825–834[Abstract]
  28. Zambon A, Deeb SS, Bensadoun A, Foster KE, Brunzell JD 2000 In vivo evidence of a role for hepatic lipase in human apoB-containing lipoprotein metabolism, independent of its lipolytic activity. J Lipid Res 41:2094–2099[Abstract/Free Full Text]
  29. Hegele RA, Little JA, Vezina C, Maguire GF, Tu L, Wolever TS, Jenkins DJA, Connelly PW 1993 Hepatic lipase deficiency. Clinical, biochemical, and molecular genetic characteristics. Arterioscler Thromb 13:720–728[Abstract/Free Full Text]
  30. Wittmaack FM, Gafvels ME, Bronner M, Matsuo H, McCrae KR, Tomaszewski JE, Robinson SL, Strickland DK, Strauss III JF 1995 Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport. Endocrinology 136:340–348[Abstract]
  31. Arbogast BW, Leeper SC, Merrick RD, Olive KE, Taylor RN 1994 Which plasma factors bring about disturbances of endothelial function in pre-eclampsia. Lancet 343:340–341[CrossRef][Medline]



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Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals