Therapeutic effects of anticoagulant agents on preeclampsia in a murine model induced by phosphatidylserine/phosphatidylcholine microvesicles.
Preeclampsia (PE) is a placenta-mediated pregnancy complication that results in high maternal and neonatal mortality and morbidity worldwide. Currently, there is no satisfactory pharmacotherapeutic treatment to stop the PE progression. In this study, we investigated the therapeutic effects of anticoagulant agents, including annexin V, heparin, and a fusion protein of annexin V and hirudin (AND), in a murine PE model induced by intravenous injection of phosphatidylserine/phosphatidylcholine (PS/PC) microvesicles. Compared with the control pregnant animals, the pregnant mice injected with PS/PC presented PE-like symptoms, including elevated systolic blood pressure, proteinuria, and reduction of antithrombin III and blood platelets. However, the PE-like symptoms were significantly alleviated after the PS/PC-injected mice were treated with annexin V, AND, or heparin. Furthermore, fibrin deposition in the placentas in the anticoagulant treated mice was remarkably improved, compared with that in the mice injected with PS/PC alone. The data demonstrate that anticoagulants are effective to prevent the occurrence of PE in the murine model and also suggest that hypercoagulation in the placenta is a contributing factor in the pathogenesis of PE.
Zhang
Y
Y
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, China.
Hua
Z
Z
Zhang
K
K
Meng
K
K
Hu
Y
Y
D000818:Animals; D017304:Annexin A5 / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D000990:Antithrombin III / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D005313:Fetal Death / Q000139:chemically induced / Q000473:pathology; D020567:Fetal Weight / Q000187:drug effects; D005337:Fibrin / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D024764:Hirudin Therapy; D006629:Hirudins / Q000009:adverse effects / Q000494:pharmacology; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000008:administration & dosage / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010976:Platelet Count; D011225:Pre-Eclampsia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011247:Pregnancy; D011507:Proteinuria / Q000517:prevention & control / Q000652:urine
D017304:Annexin A5; D000925:Anticoagulants; D006629:Hirudins; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D000990:Antithrombin III; D005337:Fibrin; D006493:Heparin