Long-chain fatty acid oxidation changes in a β2 glycoprotein I-induced preeclampsia-like mouse model.
BACKGROUND
Abnormal fatty acid oxidation (FAO) and lipid metabolism have been found related to preeclampsia (PE). Antiphospholipid syndrome (APS) as a clinical risk factor for PE has also been reported with abnormal lipid metabolism. However, the role of FAO in PE accompanied with APS is unknown. We aimed to investigate long-chain FAO changes in a PE-like rodent model induced by beta 2-glycoprotein I (β2GPI).


METHODS
The PE-like model was established by injection of β2GPI (β2GPI group) or normal saline (control group) into C57BL/6J mice which were sacrificed on day 14 or 18 of gestation. Serum levels of anti-cardiolipin antibodies (aCL), anti-β2GPI antibodies (aβ2GPI) and serum lipids were assayed. Lipid deposition in the placenta and maternal liver was detected by lipid staining. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) mRNA and protein expression in the placenta and maternal liver was analyzed.


RESULTS
The β2GPI group showed PE-like symptoms including hypertension, proteinuria and adverse pregnancy outcomes. Serum aCL, aβ2GPI, free fatty acid (FFA) and triglyceride (TG) levels in the β2GPI group were significantly elevated compared with the corresponding control group (P < 0.05), while cholesterol showed no significant changes. Placenta and maternal liver fatty infiltration was found in the β2GPI group. LCHAD mRNA and protein expression in the placenta and maternal liver in the β2GPI group were significantly elevated compared with the corresponding control group (P < 0.05).


CONCLUSIONS
β2GPI can induce PE-like symptoms, elevated serum FFA and TG, and abnormal LCHAD expression in pregnant mice. Changes in long-chain FAO could be a factor linking PE and APS.
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, PR China.
X
X
Ding
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: zi_yang@email.com.
Z
Z
Yang
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, PR China.
Y
Y
Han
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, PR China.
H
H
Yu
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism; D002308:Cardiolipins / Q000276:immunology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006973:Hypertension; D050356:Lipid Metabolism; D008099:Liver / Q000737:chemistry / Q000473:pathology; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010920:Placenta / Q000737:chemistry / Q000473:pathology; D011225:Pre-Eclampsia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011507:Proteinuria; D012333:RNA, Messenger / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D053482:beta 2-Glycoprotein I / Q000008:administration & dosage* / Q000276:immunology
D017152:Antibodies, Antiphospholipid; D002308:Cardiolipins; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D014280:Triglycerides; D053482:beta 2-Glycoprotein I; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
Antiphospholipid syndrome; Fatty acid oxidation; Preeclampsia