Yael Einbinder1,2, Tal Biron-Shental2,3, Moran Agassi-Zaitler3, Keren Tzadikevitch-Geffen2,3, Jacob Vaya4, Soliman Khatib4, Meital Ohana1, Sydney Benchetrit1,2, Tali Zitman-Gal5,6. 1. Department of Nephrology and Hypertension, Meir Medical Center, 44281, Kfar Saba, Israel. 2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel. 4. Laboratory of Oxidative Stress and Human Diseases, Migdal-Galilee Technology Center, Tel Hai College, Kiryat Shmona, Israel. 5. Department of Nephrology and Hypertension, Meir Medical Center, 44281, Kfar Saba, Israel. tali.gal@clalit.org.il. 6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. tali.gal@clalit.org.il.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: 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.