Page 8 - K. Development and regeneration

[K. Development and regeneration-6]

Hydroxychloroquine modifies features of preeclampsia (PE)

phenotype in L-nitro-arginine methyl ester (L-NAME)

induced-PE rat model

Minji Choi¹˙²˙³, Jae Ryoung Hwang², Nagyeong Byun²˙³, Suk-Joo Choi³, Soo-young Oh³, Jung-Sun Kim⁴,

Cheong-Rae Roh³˙*

¹Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 16419, Korea, Republic

of, ²Samsung biomedical research institute, Samsung Medical Center, Seoul 06351, Korea, Republic of,
³Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of
Medicine, Seoul 06351, Korea, Republic of, ⁴Department of Pathology and Translational Genomics, Samsung

Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea, Republic of

Hydroxychloroquine(HCQ), known as an antimalarial drug, has been widely used to treat lupus even during

pregnancy. In a recent clinical study, our team confirmed that HCQ significantly decreased the risk of preeclampsia
(PE), to below 80%, in pregnant women with lupus(Lupus 2019;28:722-730). However, the underlying mechanism of

HCQ of decreasing risk of PE is not clear. In this study, we investigated how HCQ affects on the features of PE
phenotype using L-NAME induced-PE rat models. Pregnant SD rats were divided into four groups; 1) control, 2) L-

NAME group in which L-NAME(300 mg/L) in drinking water was administrated from GD 7 to 18, 3) HCQ group in
which daily oral HCQ (10 mg/kg/day) was administrated from GD 7 to 18, and 4) L-NAME plus HCQ group. Our

data showed HCQ significantly decreased systolic blood pressure(149.4-152.4 to 138.5-142.1 mmHg, GD12-16,
P<0.05) and tended to alleviate fetal resorption(23.1 to 13.4 %, P=0.16) in PE rat model. HCQ mitigated plasma
level of sFlt-1(63.0 to 47.8 pg/ml, P<0.05) and endothelin-1(0.61 to 0.45 pg/ml, P<0.01) but not PlGF, TNF-a and IL-

6. Our study showed that HCQ mitigated L-NAME induced-hypertension, fetal resorption, elevation of plasma sFlt-

1 and ET-1 in PE rat model, suggesting endothelial protective mechanism of HCQ.