Pathophysiology of preeclampsia and rationale for heparin-mediated extracorporeal low-density lipoprotein precipitation as a possible therapeutic approach [Elektronische Ressource] / vorgelegt von Ying Wang

Wang Lunyue, Tse Ying

Description

Pathophysiology of Preeclampsia and Rationale for Heparin-mediated Extracorporeal Low-density Lipoprotein Precipitation as a Possible Therapeutic Approach Presented by Ying Wang Yantai, P. R. China 2004 1Aus dem Institut für Klinische Chemie der Ludwig-Maximilians-Universität München Direktor: Prof. Dr. med. Dr. h. c. Dietrich Seidel Pathophysiology of Preeclampsia and Rationale for Heparin-mediated Extracorporeal Low-density Lipoprotein Precipitation as a Possible Therapeutic Approach Dissertation Zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München vorgelegt von Ying Wang Yantai, P. R. China 2004 2Mit Genehmigung der Medizinischen Fakultät der Universität München Berichterstatter: Prof. Dr. rer. nat. Dr. med. habil. Autar K. Walli Prof. Dr. D. Schlöndorff Mitberichterstatter: Prof. Dr. F. Kainer Prof. Dr. R. Lorenz Dekan: Prof. Dr. med. Dr. h. c. K. Peter Tag der mündlichen Prüfung: 13. 05. 2004 3Preface I am indebted to Prof. Dr. med. Dr. h. c. Dietrich Seidel for giving me the opportunity to realize this work and for his encouragement and suggestions. I thank PD. Dr. Uwe Hasbargen for his cooperation and helpful suggestions in this study.

Sujets

• Gesundheit

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2004
• Nombre de lectures: 27
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

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Pathophysiology of Preeclampsia and Rationale for Heparin-mediated Extracorporeal Low-density Lipoprotein Precipitation as a Possible Therapeutic Approach         

 Presented by Ying Wang Yantai, P. R. China 2004 

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Aus dem Institut für Klinische Chemie der Ludwig-Maximilians-Universität München Direktor: Prof. Dr. med. Dr. h. c. Dietrich Seidel     Pathophysiology of Preeclampsia and Rationale for Heparin- mediated Extracorporeal Low-density Lipoprotein Precipitation as a Possible Therapeutic Approach   Dissertation Zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München

vorgelegt von Ying Wang Yantai, P. R. China 2004

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Mit Genehmigung der Medizinischen Fakultät

der Universität München

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Berichterstatter: Prof. Dr. rer. nat. Dr. med. habil. Autar K. Walli

 Prof. Dr. D. Schlöndorff

Mitberichterstatter: Prof. Dr. F. Kainer

 Prof. Dr. R. Lorenz

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Dekan: Prof. Dr. med. Dr. h. c. K. Peter

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Tag der

mündlichen Prüfung: 13. 05. 2004

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Preface

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I am indebted to Prof. Dr. med. Dr. h. c. Dietrich Seidel for giving me

the opportunity to realize this work and for his encouragement and

suggestions.

I thank PD. Dr. Uwe Hasbargen for his cooperation and helpful

suggestions in this study.

Iappreciatethehelpgiventomeatvariousstagesby

Dr. P. Fraunberger, Dr. F. Blessing, Mrs. Astrid Heim, Mrs. B. Siegle,

and nurses from H.E.L.P. station (Mrs. I. Jacobsen, Mrs. M. Schuster,

Mrs. E. Worm, Mrs. C. Hanst).

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Finally I would like to express my thanks to Prof. Dr. Autar K. Walli

for supervising this work and critical advice.

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Index of Content 

 Preface  1. Introduction  1.1. Human Placenta 1.2.Normalplasmalipoproteinmatabolism  1.3. Alterations in lipoproteins, coagulatory factors and  proinflammatory markers in preeclampsia  1.4a. Summary of existing information and purpose of the  present study  1.4b.ztesleiZgun 2. Methods  2.1. Subjects  2.2. Sampling  2.2.1. Blood collection  2.2.2. Placental tissue  2.3. Mononuclear cells  2.4. Serum lipids and lipoproteins  2.5. Lipoprotein isolation  2.6. H.E.L.P. therapy procedure  2.7. Immunohistochemical techniques  2.8. Transcription factors  2.8.1. DNA binding assay for NF-κB  2.8.2. DNA binding assay for AP-1

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 2.9. Analytical techniques  2.10. Statistical analysis 3. Results 3.1.ModulationofproatherogenicfactorsbyH.E.L.P.therapy  3.2. Plasma lipids, lipoproteins and proinflammatory markers  in normal pregnant women and preeclamptic patients  3.3. Circulating levels of lipids, lipoproteins and  proinflammtory markers in placental blood from normal  pregnant women and preeclamptic patients  3.4. Ameliorative effects of H.E.L.P.-apheresis in preeclamptic  patients  3.4.1. Case reports  3.4.2. Reduction of lipoproteins, fibrinogen and hs-CRP by  H.E.L.P. therapy  3.4.3. Proinflammatory markers  3.4.4. Procoagulatory factors and plasma viscosity  3.4.5. Return of fibrinogen levels after H.E.L.P. therapy  3.4.6. Plasma viscosity  3.4.7. Modulation of proinflammatory status in placental tissue  and maternal PBMC  3.4.7.1. Immunohistochemical studies  3.4.7.2. EMSA analysis of NF-κB and AP-1 DNA binding  activity  3.4.8. Modulation of proinflammatory status in maternal  PBMC

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4. Discussion

5a. Summary

5b. Zusammen

5b. Zusammenfassung

6. Index of literature

7. Glossary

8. Curriculum Vitae

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1. Introduction  Preeclampsia is a form of hypertension in pregnancy causing both increased maternal and fetal morbidity and mortality. It affects 210% nulliparas and is more prevalent when preexisting conditions such as hypertension, renal disease, or diabetes are present (August, 2000). Severe preeclampsia in pregnant women is characterized by hypertension, proteinuria, oligouria, eclampsia seizures, pulmonary edema, hepatic rupture, impaired liver function, thrombocytopenia and disseminated intravascular coagulation (Antoinette et al., 2001). Risks to the fetus include growth retardation, placental abruption and death. A major complication in some cases is characterized by hemolysis, elevated liver enzymes and low platelet count (HELLP syndrome), which is a serious, life-threatening form of preeclampsia. The incidence of HELLP syndrome has been reported to be around 0.17 0.85% of all live births (Rath, 2000), resulting in increased postpartum maternal morbidity and serious manifestations of severe preeclampsia. Till today there is no satisfactory treatment for preeclampsia except for immediate removal of the trophoblast, resulting in discontinuation of pregnancy. Prolongation of pregnancy is, in theory, favorable for the fetus but deleterious for the mother. Decisions regarding the need for treatment and the selection of specific measures should be based on assessment of relative benefits and risks for the individual mother and her fetus. Endothelial cell activation or dysfunction appears to be mainly responsible in the pathogenesis of preeclampsia. Factors leading to endothelial dysfunction include placental ischemia, lipoprotein induced toxicity, oxygen free radicals, immune maladaptation resulting in synthesis and release of proinflammatory cytokines. Placenta, which is a heterogeneous organ, is composed of various cell types. Placental disorders, which are encountered in preeclampsia, bear similarity to the process of atherogenesis. Therefore each of these aspects will be described briefly.   1.1. Human placenta:  Human placenta is a heterogeneous organ, connecting maternal decidua with basal plate, and through umbilical vessels establishing its