TY - JOUR
T1 - Vitamin B3 nicotinamide
T2 - A promising candidate for treating preeclampsia and improving fetal growth
AU - Takahashi, Nobuyuki
AU - Li, Feng
AU - Fushima, Tomofumi
AU - Oyanagi, Gen
AU - Sato, Emiko
AU - Oe, Yuji
AU - Sekimoto, Akiyo
AU - Saigusa, Daisuke
AU - Sato, Hiroshi
AU - Ito, Sadayoshi
N1 - Funding Information:
We thank H.W. Davin Townley-Tilson, Hironobu Nakada, John R. Hagaman, Jennifer Wilder, and Manyu Li, J. Charles Jennette, Nobuyo Maeda, and Oliver Smithies. Our work was supported by a Grant-In-Aid from the Japan Society of Promotion of Science (JSPS, 24659409), Translational Research Network Program of Ministry of Education, Culture, Sports, Science and Technology of Japan (J140001192), a major grant from the National Institutes of Health (HL049277), funds from the Department of Pathology and Laboratory Medicine at UNC Chapel Hill, the Naito Foundation and Miyagi Kidney Foundation.
Funding Information:
Our work was supported by a Grant-In-Aid from the Japan Society of Promotion of Science (JSPS, 24659409), Translational Research Network Program of Ministry of Education, Culture, Sports, Science and Technology of Japan (J140001192), a major grant from the National Institutes of Health (HL049277), funds from the Department of Pathology and Laboratory Medicine at UNC Chapel Hill, the Naito Foundation and Miyagi Kidney Foundation.
Publisher Copyright:
© 2018 Tohoku University Medical Press.
PY - 2018/3
Y1 - 2018/3
N2 - 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 B3 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.
AB - 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 B3 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.
KW - Endotheliosis
KW - Fetal growth restriction
KW - Nicotinamide
KW - Preeclampsia
KW - Premature delivery
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U2 - 10.1620/tjem.244.243
DO - 10.1620/tjem.244.243
M3 - Review article
C2 - 29563389
AN - SCOPUS:85045219165
SN - 0040-8727
VL - 244
SP - 243
EP - 248
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
IS - 3
ER -