Fumitomo Nishimura

Decreased Lectin-Like Oxidized LDL Receptor 1 (LOX-1) and Low Nrf2 Activation in Placenta Are Involved in Preeclampsia

CONTEXT Serum concentration of oxidized low-density lipoprotein (oxLDL) is higher in women with preeclampsia than in normal pregnant woman. Lectin-like oxLDL receptor-1 (LOX-1) is one of the scavenger receptors for oxLDL and is abundantly expressed in placenta. It is well known that oxLDL activates nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant and cytoprotective genes such as heme oxygenase-1 (HO-1), which play an important role in preeclampsia. However, it has yet to be elucidated whether LOX-1, along with Nrf2, participates in the pathology of preeclampsia. OBJECTIVE The objective of the study was to assess LOX-1 expression and Nrf2 activation in preeclamptic placentas and to manifest their physiological roles in preeclampsia. METHODS Expression and regulation of LOX-1, HO-1, and Nrf2 were evaluated by real-time quantitative RT-PCR and Western blotting. The functions of LOX-1 and Nrf2 were examined using an anti-LOX-1 antibody and Nrf2 activator in JAR, a choriocarcinoma cell line, and placental explants. RESULTS Both LOX-1 expression and Nrf2 activation were significantly decreased in preeclamptic placentas compared with normal controls. A significant decrease in LOX-1 mRNA was found in placental explant cultures under hypoxic conditions. Activation of Nrf2 up-regulated HO-1 in both the JAR cells and placental explants. Furthermore, oxLDL increased HO-1 mRNA, whereas the blockade of LOX-1 inhibited the increase of HO-1 mRNA in JAR cells. CONCLUSION Decreasing LOX-1 expression in preeclamptic placenta may contribute to high oxLDL concentration, low Nrf2 activation, and low HO-1 expression. These findings provide novel insights into the crucial role of LOX-1 and Nrf2 in the pathogenesis of preeclampsia.

ATP-binding cassette transporter A1 expression is decreased in preeclamptic placentas.

Preeclampsia is a pregnancy-specific multisystem disorder characterized by hypertension and proteinuria. Accentuated maternal hyperlipidemia, especially high serum levels of oxidized low-density lipoprotein (oxLDL), is one of the features of preeclampsia. We previously reported that lectin-like oxidized LDL receptor 1 (LOX-1) expression was decreased in preeclamptic placentas. Here, we show that decreased LOX-1 expression is associated with low expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) in the placenta. The ABCA1 mediates cellular efflux of cholesterol, and liver X receptors (LXRs) are its predominant transcriptional regulators. Both ABCA1 and LXR expressions were significantly lower in preeclamptic placentas than those in normal controls. Oxidized LDL upregulated ABCA1 expression, while LOX-1 blockade resulted in the alleviation of increasing ABCA1 messenger RNA in JAR cells. These results suggest that low LOX-1 expression may lead to insufficient oxLDL uptake, thereby contributing to reduced LXR activation and decreased ABCA1 expression in preeclamptic placentas.

Association between Premenstrual Syndrome and Daily Physical Activity Levels

Objective: The purpose of this study was to investigate the association between premenstrual syndrome (PMS) and daily physical activity. Methods: Three hundred forty-nine women (18-50 years) were analyzed. We investigated body mass index, PMS symptoms, physical activity level, and some factors related to PMS (age, sleep time, caffeine intake, alcohol intake, smoking status). Participants were grouped according to physical activity level into low, normal, and high physical activity groups. Binominal logistic regression analysis was used to examine the association between PMS and daily physical activity level. Results: The average physical activity levels of the low, normal and high physical activity groups were 301.4 ± 233.8 kcal, 975.0 ± 187.3 kcal, and 4558.7 ± 3798.5 kcal, respectively. The incidence of PMS was higher in both the low physical activity group (OR=2.45, 95% CI=1.18-5.11) and high physical activity group (OR=2.13, 95% CI=1.01-4.50) than in the normal physical activity group. Conclusion: PMS rates were higher in women who have either low or high daily physical activity levels than in those with normal physical activity levels. Therefore, women should be advised to avoid inactivity or excessive daily physical activity.