High-density lipoproteins (HDL) composition and function in preeclampsia
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To evaluate (a) the properties of high-density lipoproteins (HDL)/cholesterol, which include apolipoprotein A-1 (ApoA1) and paraoxonase1 (PON1), both are negative predictors of cardiovascular risk and (b) HDL function, among women with preeclampsia (PE). PE is a multi-system disorder, characterized by onset of hypertension and proteinuria or other end-organ dysfunction in the second half of pregnancy. Preeclampsia is associated with increased risk for later cardiovascular disease. The inverse association between HDL, cholesterol levels and the risk of developing atherosclerotic cardiovascular disease is well-established.
Twenty-five pregnant women [19 with PE and 6 with normal pregnancy (NP)] were recruited during admission for delivery. HDL was isolated from blood samples. PON1 activity and HDL were analyzed. An in vitro model of endothelial cells was used to evaluate the effect of HDL on the transcription response of vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) mRNA expression.
PON1 activity (units/ml serum) was lower in the PE group compared to normal pregnancy (NP) (6.51 ± 0.73 vs. 9.98 ± 0.54; P = 0.015). Increased ApoA1 was released from PE-HDL as compared to NP-HDL (3.54 ± 0.72 vs. 0.89 ± 0.35; P = 0.01). PE-HDL exhibited increased VCAM-1 mRNA expression and decreased eNOS mRNA expression on TNF-α stimulated endothelial cells as compared to NP-HDL.
HDL from women with PE reduced PON1 activity and increased ApoA1 release from HDL particles. This process was associated with increased HDL diameter, suggesting impaired HDL anti-oxidant activity. These changes might contribute to higher long-term cardiovascular risks among women with PE.
KeywordsPreeclampsia HDL ApoA1 PON1 eNOS VCAM-1
This study is part of the basic science requirements of M. Agassi-Zaitler, Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel. We thank the delivery room staff of Meir Medical Center for helping recruit women to the study. We thank Prof. M. Aviram and N. Volkova from the Lipid Research Laboratory Technion, Rappaport Faculty of Medicine, Rambam Medical Center, Haifa, Israel for teaching us the HDL isolation method. We thank D. Atrahimovich from the Laboratory of Oxidative Stress and Human Diseases in the Migdal-Galilee Technology Center, Israel for helping with the PON1 activity assay. We thank F. Schreiber, MSc for editing the manuscript and N. Jelin, MA for assistance with the statistical analysis. They are both employees of Meir Medical Center.
YE, TBS, JV, SB and TZG conception and design of research; YE, KTG, MAZ and TZG data and blood collection; MO, KTG, MAZ, SK and TZG performed experiments; TZG, MO and SK analyzed data, interpreted results and prepared figures; YE, TBS, JV, SB and TZG drafted manuscript; YE, SB and TZG edited and revised manuscript; all authors approved the final version of manuscript.
This work was supported by the Mintz-Law Foundation (Y. Einbinder) from the Sackler Faculty of Medicine, Tel Aviv University, Israel.
Compliance with ethical standards
Conflict of interest
All authors have no conflicts of interest.
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