Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences.
Department of Medicine, Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University.
Tohoku J Exp Med. 2018 Mar;244(3):243-248. doi: 10.1620/tjem.244.243.
Up to 8% of pregnant women suffer from preeclampsia (PE), a deadly disease characterized by high blood pressure (BP), blood vessel damage, called endotheliosis (vascular endothelial swelling with narrowing of capillary lumen), and high levels of protein in the urine. PE is often associated with premature delivery, which is a risk factor of cardiovascular and metabolic diseases among the offspring. Accordingly, establishing drug treatments of PE is in immediate needs. Currently, many of anti-hypertensive drugs cause malformation of the fetuses and are contraindicated for pregnant women. Anti-hypertensive drugs that are allowed to be used for treating pregnant women could lower BP of the mothers and reduce the risk of maternal death due to cardiovascular diseases such as cerebral hemorrhage. However, these anti-hypertensives do not improve endotheliosis and proteinuria. In fact, they reduce blood supply to the placentae and fetuses, which could lead to fetal growth restriction (FGR) and fetal and neonatal death. Until now, the only treatment for preeclamptic women has been delivery of the baby and placenta. Using three mechanistically different mouse models of PE, we have found that vitamin B nicotinamide (Nam) is the first safe drug that alleviates PE, and that Nam also alleviates or prevents miscarriage, prolongs pregnancy period, and improves the growth of the fetuses in mice with PE. Importantly, Nam has been used for pregnant and nursing women who have difficulty in taking sufficient meal. Nam could help treat or prevent PE and FGR associated with PE, if the treatment works in humans.
多达 8%的孕妇患有子痫前期 (PE)，这是一种致命的疾病，其特征是高血压 (BP)、血管损伤，称为内皮细胞病（血管内皮肿胀伴毛细血管腔变窄）以及尿液中高水平的蛋白质。PE 常与早产有关，而早产是后代心血管和代谢疾病的一个风险因素。因此，立即需要建立针对 PE 的药物治疗方法。目前，许多抗高血压药物会导致胎儿畸形，因此不适合孕妇使用。允许用于治疗孕妇的抗高血压药物可以降低母亲的血压，并降低因脑出血等心血管疾病导致的母亲死亡风险。然而，这些抗高血压药物并不能改善内皮细胞病和蛋白尿。事实上，它们会减少胎盘和胎儿的血液供应，从而导致胎儿生长受限 (FGR) 和胎儿及新生儿死亡。到目前为止，子痫前期妇女的唯一治疗方法是分娩婴儿和胎盘。我们使用三种机制不同的 PE 小鼠模型发现，维生素 B 烟酰胺 (Nam) 是第一种可缓解 PE 的安全药物，并且 Nam 还可缓解或预防流产，延长妊娠周期，并改善 PE 小鼠中胎儿的生长。重要的是，Nam 已被用于难以摄入足够膳食的孕妇和哺乳期妇女。如果在人类中有效，Nam 可能有助于治疗或预防与 PE 相关的 PE 和 FGR。
