Lipid metabolism and endothelial cell dysfunction in women with preeclampsia Ayumi TANAKA, Hajime MORIKAWA*, Mineo YA1VIASAKI*, Matsuto MOCHIZUKI Depa
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1 Lipid metabolism and endothelial cell dysfunction in women with preeclampsia Ayumi TANAKA, Hajime MORIKAWA*, Mineo YA1VIASAKI*, Matsuto MOCHIZUKI Department of Obstetrics and Gynecology, Kobe University School of Medicine, Kobe, Japan *Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Japan Recent studies have focused on endothelial dysfunction as a cause of preeclampsia. From the perspective of cardiovascular research, there is increasing evidence that hyperlipidemia can cause endothelial dysfunction. We have therefore raised the question whether the alterations in lipid metabolism have any role in the pathophysiology of preeclampsia. Participants were 128 normal pregnant women and 37 women with the disorder. All of them were in the 3rd trimester of pregnancy. To clarify the effect of lipids on the endothelial cells, we use cultured human pulmonary arterial endothelial cells. Cell injuries were quantified with the Fura-2 method (Abe, 1988.) The results are as follows. 1. Serum lipid analysis Serum levels of triglycerides were significantly elevated and the levels of HDL-cholesterol were significantly depressed in women with preeclampsia compared with normal pregnant subjects. The atherogenic index was significantly higher in the preeclamptic patients than in the control group. Serum levels of lipidperoxides were significantly higher, while the levels of vitamin E were lower in the hypertensive pregnant patients. The P/S ratio of total lipids was significantly lower and the EPA/AA ratio in serum was lower in the patients with preeclampsia compared with the normal pregnant women. 2. Lipid treatment and endothelial cell damage in vitro study Both LPC (a major component of the oxidized LDL) and t-bhp (one of the lipidperoxides) damaged membranes indicated by an increase of specific releases of Fura-2 trapped in cytoplasm into culture media. However, HDL inhibits the injurious effects of these lipids. From these results it is suggested that the alterations in lipid metabolism observed in women with preeclampsia influence the onset and maintenance of hypertension in pregnancy causing atherosclerosis, endothelial cell injuries and a dysfunctional cascade of coagulation. Keywords: lipid metabolism, preeclampsia, endothelial dysfunction, atherosis, fatty acid composition
2 Table 1 Results of descriptive variables. (mean } SD)
3
4 Fig.1 Mean values of parameters in lipidmetabolism in normal pregnancy compared with those in preeclampsia in the third trimester. (mean ± SD) Table 2 Fatty acid composition of total lipids in serum expressions as mean } SD (w/w%)
5 Table 3 Effects of LPC on specific release of Fura 2 (mean ± SD%) * p<0.03 vs 10 ƒêm LPC incubated for 60min and 15ƒÊM LPC incubated for 180min ** p<0.02 vs 5 ƒêm LPC incubated for 180min
6 Fig. 2 Effects of HDL on Fura-2 release induced by 15ƒÊM LPC expressed mean values of duplicate studies. Fig. 3 Effects of t-bhp on Fura-2 release from human endothelial cells. Confluent monolayers loaded with Fura-2 were incubated for each time with the indicated does of t-bhp. (n=3, mean SD) *p<0.05 vs with 5ƒÊM t-bhp incubated for 60min. **p<0.05 vs with 5ƒÊM t-bhp incubated for 180min. ***p<0.05 vs with t-bhp incubated for 180min and vs with 15ƒÊM t-bhp incubated for 60min.
7 Fig. 4 Effects of HDL on Fura-2 release induced by 15ƒÊM t-bhp expressed mean values of duplicate studies.
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