Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA.
Int J Mol Sci. 2024 Aug 20;25(16):9017. doi: 10.3390/ijms25169017.
Preeclampsia is a complex pregnancy-related hypertensive disorder which poses significant risks for both maternal and fetal health. Preeclampsia affects 5-8% of pregnancies in the United States, causing a significant public health and economic burden. Despite extensive research, the etiology and pathogenesis of preeclampsia remain elusive, but have been correlated with maternal conditions such as obesity. In recent decades, the incidence of preeclampsia increased along with the prevalence of obesity among women of reproductive age. Maternal obesity has been shown to negatively affect pregnancy in almost all aspects. However, the precise mechanisms by which obesity influences preeclampsia are unclear. Ankyrin repeat and SOCS Box Containing protein 4 (ASB4) is an E3 ubiquitin ligase that can promote the degradation of a wide range of target proteins. ASB4-null mice display a full spectrum of preeclampsia-like phenotypes during pregnancy including hypertension, proteinuria, and decreased litter size. Furthermore, maternal obesity induced by a high-fat diet aggravates preeclampsia-like phenotypes in pregnant mice lacking ASB4. Variants in the ASB4 gene have been associated with obesity in humans, and a functional connection between the ASB4 gene and obesity has been established in mice. This review discusses the connections between preeclampsia, obesity, and ASB4.
子痫前期是一种与妊娠相关的复杂高血压疾病，对母婴健康都构成重大风险。子痫前期影响了美国 5-8%的妊娠，造成了显著的公共卫生和经济负担。尽管进行了广泛的研究，但子痫前期的病因和发病机制仍不清楚，但与肥胖等母体状况有关。近几十年来，随着育龄妇女肥胖症的流行，子痫前期的发病率也有所上升。肥胖已被证明几乎在所有方面都对妊娠产生负面影响。然而，肥胖影响子痫前期的确切机制尚不清楚。锚蛋白重复和 SOCS 盒富含蛋白 4（ASB4）是一种 E3 泛素连接酶，可以促进广泛的靶蛋白降解。ASB4 缺失的小鼠在妊娠期间表现出一系列子痫前期样表型，包括高血压、蛋白尿和产仔数减少。此外，高脂肪饮食诱导的母体肥胖会加重缺乏 ASB4 的妊娠小鼠的子痫前期样表型。ASB4 基因的变异与人类肥胖有关，并且在小鼠中已经建立了 ASB4 基因与肥胖之间的功能联系。这篇综述讨论了子痫前期、肥胖和 ASB4 之间的联系。
