New insights into the role of aminopeptidases in the treatment for both preeclampsia and preterm labor.
BACKGROUND
Evidence elucidating the pathophysiology and pharmacology of conventional drugs, β-2 stimulants and magnesium sulfate, on safety and effectiveness for preeclampsia and preterm labor are rarely found. Both compounds pass through the placental barrier and could exert their adverse effects on the fetus. Exposure to these agents could be problematic long after the birth, and possibly result in diseases such as autism and cardiomyopathy. Since 1970 the possible roles of placental aminopeptidases, which degrade peptide hormones, in preeclampsia and preterm labor have been studied.


METHODS
Many studies reveal that the fetus secretes peptide hormones, such as angiotensin II, vasopressin, and oxytocin, under hypoxia (stress) during the course of its growth, suggesting the critical effects these hormones have during pregnancy. The roles of placental aminopeptidases, the enzymes which degrade fetal hormones without passing through the placental barrier, were clarified. A first-step production system for recombinant aminopeptidases was established, by which engineered recombinant aminopeptidases were used for further experiments testing expected efficacy on controlling the level of hormones.


CONCLUSIONS
The authors conclude that both aminopeptidase A and placental leucine aminopeptidase could be potentially safe and effective drugs for patients and their babies in the treatment of preeclampsia and preterm labor.
Daiya Building Ladys' Clinic , 1F, No.2, 3-15-1, Meieki, Nakamura-ku, Nagoya, 450-0002 , Japan.
Shigehiko
S
Mizutani
Taihei
T
Tsunemi
Eita
E
Mizutani
Akira
A
Hattori
Masafumi
M
Tsujimoto
Hiroshi
H
Kobayashi
D000626:Aminopeptidases / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000188:drug therapy* / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism; D010920:Placenta / Q000201:enzymology; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000378:metabolism; D011247:Pregnancy
D036361:Peptide Hormones; D000626:Aminopeptidases