RSS-Feed abonnieren
DOI: 10.1055/s-0032-1323793
Untersuchungen des maternalen und fetalen Serumlipidprofils und des oxidierten ‚Low Density‘ Lipoproteins im plazentaren Gewebe bei Präeklampsie und normotensiven Schwangerschaften
Determination of Maternal and Foetal Serum Lipid Profile and Placental Oxidised Low Density Lipoprotein Accumulation in Preeclampsia and Normotensive PregnanciesPublikationsverlauf
eingereicht 02. März 2012
angenommen nach Überarbeitung 03. April 2012
Publikationsdatum:
29. Oktober 2012 (online)

Zusammenfassung
Hintergrund:
Oxidierte ‚Low Density‘ Lipoproteine (oxLDL) gelten als Schlüsselmoleküle in der Pathogenese der Atherosklerose. Da die Präeklampsie Parallelen zur Atherosklerose aufweist, gingen wir von der Hypothese einer vermehrten Anreicherung von oxLDL im plazentaren Gewebe an der materno-fetalen und feto-fetalen Grenzfläche aus. Zudem analysierten wir das Lipidprofil des mütterliches und fetales Serums bei Präeklampsie und einer Kontrollgruppe normotensiver Schwangerschaften.
Patientinnen und Methodik:
oxLDL wurde in plazentaren Paraffinschnitten von 14 Präeklampsien (30.–39. SSW) sowie 28 Früh- und Termingeburten (25.–40. SSW) immunhistochemisch dargestellt. 10 ‚High Power Fields‘ wurden mit der newCAST Software randomisiert ausgewählt und nach standardisiertem Verfahren von 2 unabhängigen Untersuchern ohne Kenntnis der Diagnosen auf die Intensität von oxLDL bewertet. Triglyzeride, Gesamt-Cholesterin, LDL- und HDL-Cholesterin wurden in mütterlichem und fetalem (Nabelschnur) Serum gemessen. Die statistische Auswertung erfolgte durch den Mann-Whitney Test.
Ergebnis:
oxLDL war sowohl im villösen Trophoblast als auch in plazentaren Endothelzellen nachweisbar. Immunhistochemisch ließen sich keine signifikanten Unterschiede in der oxLDL-Intensität in den verschiedenen Kompartimenten der Patientinnen mit Präeklampsie und unkomplizierter Schwangerschaft nachweisen. Die Serum-Triglyzeridkonzentrationen waren sowohl bei den Müttern als auch bei den Kindern nach Präeklampsie signifikant erhöht (Mutter Präeklampsie 293 [St.abw. 87,4] mg/dL, Kontrolle 214 [Stabw. 89,4] mg/dL, p=0,0097; Fet Präeklampsie 26 [St.abw. 16,6] mg/dL, Kontrolle 18 [Stabw. 10,4] mg/dL, p=0,0463). Hinsichtlich der anderen Serumparameter zeigten sich keine signifikanten Unterschiede.
Schlussfolgerung:
Unsere Hypothese einer vermehrten oxLDL Anreicherung im plazentaren Gewebe bei Präeklampsie im Vergleich zu unkomplizierten Schwangerschaften ließ sich nicht bestätigen. Wir fanden allerdings signifikante Unterschiede hinsichtlich der Triglyzeridkonzentration bei Mutter und Kind zwischen Präeklampsie und normotensivem Schwangerschaftsverlauf. Diese Untersuchungsergebnisse bieten Ansatzpunkte für weitere Studien im Rahmen der Entstehung und Programmierung kardiovaskulärer Erkrankungen bei Mutter und Kind.
Abstract
Background:
Oxidised low density lipoproteins (oxLDL) are key players in the development of atherosclerotic cardiovascular diseases. Since there are similarities between the pathogenesis of preeclampsia and atherosclerosis we hypothesised an increased accumulation of oxLDL at the materno-foetal and foeto-foetal interface within the placental tissue of preeclamptic women compared to women with normotensive pregnancies (controls). Moreover, we analysed maternal and foetal serum lipid parameters.
Patients and Methods:
oxLDL was determined by immunohistochemistry in placental paraffin sections of 14 women suffering from preeclampsia (30th–39th week of gestation) and compared to 28 preterm and term deliveries (25th–40th week of gestation). 10 high power fields were chosen randomly by the newCAST software and oxLDL expression was analysed via standardised methods by 2 independent and blinded investigators. Maternal and foetal triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol were measured. Statistical examination was carried out by the Mann-Whitney test.
Results:
oxLDL was found in villous trophoblast and placental endothelium. No significant differences were observed in expression intensity between preeclampsia and controls. Maternal and foetal triglyceride levels were significantly increased in preeclampsia compared to controls (preeclampsia mothers: 293 [SD 87.4] mg/dL, controls: 214 [SD 89.4] mg/dL, p=0.0097; preeclampsia foetuses: 26 [SD 16.6] mg/dL, controls: 18 [SD 10.4] mg/dL, p=0.0463). No significant differences in other lipid concentrations were found.
Conclusions:
We could not confirm our initial hypothesis of an increased oxLDL accumulation in placental tissue of preeclampsia. However, preeclampsia is a condition of dyslipidaemia affecting both maternal and foetal serum with implications for development and programming of cardiovascular diseases in later life.
-
Literatur
- 1 Galle J, Hansen-Hagge T, Wanner C et al. Impact of oxidized low density lipoprotein on vascular cells. Atherosclerosis 2006; 185: 219-226
- 2 Levitan I, Volkov S, Subbaiah PV. Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxid Redox Signal 2010; 13: 39-75
- 3 Bonet B, Chait A, Gown AM et al. Metabolism of modified LDL by cultured human placental cells. Atherosclerosis 1995; 112: 125-136
- 4 Byfield FJ, Tikku S, Rothblat GH et al. OxLDL increases endothelial stiffness, force generation, and network formation. J Lipid Res 2006; 47: 715-723
- 5 Dimmeler S, Haendeler J, Galle J et al. Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-like proteases. A mechanistic clue to the ‘response to injury’ hypothesis. Circulation 1997; 95: 1760-1763
- 6 Ding Z, Fan Y, Deng X. Concentration polarization of oxidative modification of low-density lipoproteins: its effect on oxidative modification of low-density lipoprotein uptake and apoptosis of the endothelial cells. Asaio J 2010; 56: 468-474
- 7 Rath W, Fischer T. The diagnosis and treatment of hypertensive disorders of pregnancy: new findings for antenatal and inpatient care. Dtsch Arztebl Int 2009; 106: 733-738
- 8 Huppertz B. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension 2008; 51: 970-975
- 9 Steegers EA, von Dadelszen P, Duvekot JJ et al. Pre-eclampsia. Lancet 2010; 376: 631-644
- 10 Belo L, Caslake M, Gaffney D et al. Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies. Atherosclerosis 2002; 162: 425-432
- 11 Hubel CA, Lyall F, Weissfeld L et al. Small low-density lipoproteins and vascular cell adhesion molecule-1 are increased in association with hyperlipidemia in preeclampsia. Metabolism 1998; 47: 1281-1288
- 12 Sattar N, Gaw A, Packard CJ et al. Potential pathogenic roles of aberrant lipoprotein and fatty acid metabolism in pre-eclampsia. Br J Obstet Gynaecol 1996; 103: 614-620
- 13 Winkler K, Wetzka B, Hoffmann MM et al. Triglyceride-rich lipoproteins are associated with hypertension in preeclampsia. J Clin Endocrinol Metab 2003; 88: 1162-1166
- 14 Raijmakers MT, Peters WH, Steegers EA et al. Amino thiols, detoxification and oxidative stress in pre-eclampsia and other disorders of pregnancy. Curr Pharm Des 2005; 11: 711-734
- 15 Miehe U, Kadyrov M, Neumaier-Wagner P et al. Expression of the actin stress fiber-associated protein CLP36 in the human placenta. Histochem Cell Biol 2006; 126: 465-471
- 16 Pecks U, Brieger M, Schiessl B et al. Maternal and fetal cord blood lipids in intrauterine growth restriction. J Perinat Med 2012; in press
- 17 Catarino C, Rebelo I, Belo L et al. Fetal lipoprotein changes in pre-eclampsia. Acta Obstet Gynecol Scand 2008; 87: 628-634
- 18 Rodie VA, Caslake MJ, Stewart F et al. Fetal cord plasma lipoprotein status in uncomplicated human pregnancies and in pregnancies complicated by pre-eclampsia and intrauterine growth restriction. Atherosclerosis 2004; 176: 181-187
- 19 Shibata E, Nanri H, Ejima K et al. Enhancement of mitochondrial oxidative stress and up-regulation of antioxidant protein peroxiredoxin III/SP-22 in the mitochondria of human pre-eclamptic placentae. Placenta 2003; 24: 698-705
- 20 Many A, Westerhausen-Larson A, Kanbour-Shakir A et al. Xanthine oxidase/dehydrogenase is present in human placenta. Placenta 1996; 17: 361-365
- 21 Matsubara S, Sato I. Enzyme histochemically detectable NAD(P)H oxidase in human placental trophoblasts: normal, preeclamptic, and fetal growth restriction-complicated pregnancy. Histochem Cell Biol 2001; 116: 1-7
- 22 Sikkema JM, van Rijn BB, Franx A et al. Placental superoxide is increased in pre-eclampsia. Placenta 2001; 22: 304-308
- 23 Walsh SW, Wang Y. Trophoblast and placental villous core production of lipid peroxides, thromboxane, and prostacyclin in preeclampsia. J Clin Endocrinol Metab 1995; 80: 1888-1893
- 24 Serdar Z, Gur E, Develioglu O et al. Placental and decidual lipid peroxidation and antioxidant defenses in preeclampsia. Lipid peroxidation in preeclampsia. Pathophysiology 2002; 9: 21
- 25 Madazli R, Benian A, Aydin S et al. The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in pre-eclampsia. J Obstet Gynaecol 2002; 22: 477-480
- 26 Hnat MD, Meadows JW, Brockman DE et al. Heat shock protein-70 and 4-hydroxy-2-nonenal adducts in human placental villous tissue of normotensive, preeclamptic and intrauterine growth restricted pregnancies. Am J Obstet Gynecol 2005; 193: 836-840
- 27 Santoso DI, Rogers P, Wallace EM et al. Localization of indoleamine 2,3-dioxygenase and 4-hydroxynonenal in normal and pre-eclamptic placentae. Placenta 2002; 23: 373-379
- 28 Pavan L, Tsatsaris V, Hermouet A et al. Oxidized low-density lipoproteins inhibit trophoblastic cell invasion. J Clin Endocrinol Metab 2004; 89: 1969-1972
- 29 Pecks U, Caspers R, Schiessl B et al. The evaluation of the oxidative state of low-density lipoproteins in intrauterine growth restriction and preeclampsia. Hypertens Pregnancy 2012; 31: 156-165
- 30 Barker DJ. Intrauterine programming of adult disease. Mol Med Today 1995; 1: 418-423
- 31 Plagemann A, Harder T, Schellong K et al. Fetal programming by disturbed intrauterine environment – fundamental mechanisms exemplified by the regulation of body weight and metabolism. Gynakol Geburtshilfliche Rundsch 2008; 48: 215-224