Researchers Reveal Novel Functional Properties of APOBEC3A Regulating Lipid Metabolism Associated with the Pathogenesis of Preeclampsia

Preeclampsia (PE) is a pregnancy-specific complication characterized by hypertension, proteinuria and edema that affects 3% to 8% of pregnant women worldwide. It remains one of the leading causes of maternal and perinatal mortality and morbidity. The pathogenesis of PE has not been fully elucidated yet, and the clinical management is mainly focusing on symptomatic treatment. PE tends to run in families, and a subset of PE patients showed dysfunctional lipid metabolism before clinical symptoms. Research on genetic factors and abnormal lipid metabolism in the pathogenesis of PE would contribute to understanding the complex pathogenesis of PE and provide a basis for clinical intervention in high-risk groups.

In a study published in Frontiers in Cardiovascular Medicine on May 16, a team of researchers led by GONG Likun from the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, and WANG Bingshun from the Clinical Research Institute of Shanghai Jiao Tong University School of Medicine, in collaboration with LIN Jianhua, from the Department of Obstetrics and Gynecology, Renji Hospital, CHEN Yan and GUO Yuna from the Department of Obstetrics, International Peace Maternity and Child Health Hospital, identified novel functional properties of APOBEC3A in regulating lipid metabolism from the perspective of genomic copy number variations, and that aberrant copies of APOBEC3A may be involved in the pathogenesis of PE.

The researchers observed that the total cholesterol (TC) and triglycerides (TG) of PE patients were higher than those of women with normal pregnancies in the early pregnancy; the abnormal lipid profile was associated with increased copies of APOBEC3A in pregnant women. In vitro and in vivo studies revealed that APOBEC3A overexpression resulted in elevated TC and TG levels in the host and dysregulated expression of genes related to lipid biosynthesis and catabolism. Meanwhile, mice with hepatic-specific overexpression of APOBEC3A exhibited PE-related alterations during gestation, such as reduced fetal weight and aberrant placental function. These findings indicate that APOBEC3A may be involved in the pathogenesis of PE by regulating lipid metabolism.

APOBEC3A is a nucleic acid-modifying enzyme that belongs to the cytidine deaminase family. It plays a role in mutagenesis of the host genome and defense against foreign viruses. This study reported that APOBEC3A has a regulatory role in lipid metabolism, and its increased copies may be involved in the pathogenesis of PE. This study established a novel link between genetics and lipid metabolism in the pathogenesis of PE and expanded the understanding of the complex pathogenesis of PE.

Identification and validation of APOBEC3A’s role in regulating lipid metabolism in PE (Image by GONG and WANG's collaborative team)





DIAO Wentong

Shanghai Institute of Materia Medica, Chinese Academy of Sciences