Activated protein C prevents development of phosphatidylserine-induced intrauterine growth restriction in mice.

Abstract

We examined the effect of activated protein C (APC) on the development of intrauterine growth restriction (IUGR) in an experimental animal model we established. The IUGR in mice was induced by artificial phosphatidylserine (PS)/phosphatidylcholine (PC) microvesicles that represent procoagulant phospholipids derived from activated platelets. This model represents the placental insufficiency associated with the phospholipid-induced hypercoagulable state in placental circulation. APC prolonged the activated partial thromboplastin time (aPTT) using mouse plasma and dose dependently inhibited thrombin generation in a chromogenic assay in defibrinated plasma of mice. Administration of exogenous APC at concentrations that maximally inhibited thrombin generation in defibrinated plasma prevented a significant reduction in fetal body weight and induced marked histological changes including congestion and fibrin depositions in IUGR mouse placentas. These results suggest that the inhibition of thrombin generation in the placental circulation by APC prevents the development of IUGR that is dependent on coagulation associated with PS/PC from activated platelets.