Abstract
BackgroundLong-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression is decreased in placenta of some cases of preeclampsia (PE) which may result in free fatty acid (FFA) increased. High FFA level will induce oxidative stress, so abnormal long-chain fatty acid-oxidation may participate in the pathogenesis of PE through oxidative stress pathway.MethodsPE-like groups were ApoC3 transgenic mice with abnormal fatty acid metabolism, classical PE-like models with injection of Nw-nitro-L-arginine-methyl ester (L-NA) or lipopolysaccharide (LPS) and the antiphospholipid syndrome (APS) mouse model with β2GPI injection (ApoC3+NS, ApoC3+L-NA, L-NA, LPS and β2GPI groups). The control group was wild-type mice with normal saline injection. Except for β2GPI mice, the other mice were subdivided into pre-implantation (Pre) and mid-pregnancy (Mid) subgroups by injection time.ResultsAll PE-like groups showed hypertension and proteinuria except ApoC3+NS mice only showed hypertension. Serum FFA levels increased significantly except in LPS group compared to controls (P<0.05). LCHAD mRNA and protein expression in the liver and placenta was significantly higher for ApoC3+NS, ApoC3+L-NA and β2GPI mice and lower for L-NA mice than controls (P<0.05) but did not differ between LPS mice and controls. P47phox mRNA and protein expression in the liver significantly increased in all PE-like groups except LPS group, while P47phox expression in the placenta only significantly increased in L-NA and β2GPI groups.ConclusionsAbnormal long-chain fatty acid-oxidation may play a different role in different PE-like models and in some cases participate in the pathogenesis of PE through oxidative stress pathway.
Highlights
Preeclampsia (PE) affects 5% to 8% of pregnancies and has severe consequences for both the mother and fetus [1]
Confirmation of PE models Mice in ApoC3+NS only exhibited mild gestational hypertension, but after L-NA injection, the mean arterial pressure (MAP) and urinary protein levels were higher for ApoC3+L-NA than ApoC3+NS mice (P,0.05), with PE-like symptoms (Fig. 1A,B)
We found free fatty acid (FFA) levels were significantly negatively correlated with Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) mRNA and protein expression in ApoC3+NS, ApoC3+L-NA and L-NA mice (P,0.05) and positively correlated in b2GPI mice in the liver (P,0.05), not correlated in LPS mice (Table S1)
Summary
Preeclampsia (PE) affects 5% to 8% of pregnancies and has severe consequences for both the mother and fetus [1]. We and other researchers found decreased LCHAD expression in some cases of PE without LCHAD deficiency and the expression of LCHAD significantly differed between early-onset severe PE and late-onset PE [5,6]. The heterogeneity of PE has been gradually realized by study of different etiological factors between early- and late-onset PE [7,8]. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression is decreased in placenta of some cases of preeclampsia (PE) which may result in free fatty acid (FFA) increased. High FFA level will induce oxidative stress, so abnormal long-chain fatty acid-oxidation may participate in the pathogenesis of PE through oxidative stress pathway
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