Decreased fibrinolytic capacity has been sug-

Mouse vitronectin (Vn) was isolated from serum by heparin affinity chromatography. The purified protein (Mr 71,000) supported adhesion of mouse and human cells in an Arg-Gly-Asp-dependent manner and bound to type 1 plasminogen activator inhibitor with kinetics similar to those observed using human and bovine Vn. To further characterize murine Vn and its biosynthesis in vivo, a mouse Vn cDNA was isolated from a liver cDNA library. The amino acid sequence of mouse Vn was deduced from the cDNA and was aligned with that of human Vn. Based on this alignment, mouse Vn was inferred to be 457 amino acids long and to have extensive (82%) homology with human Vn. Northern blot hybridization analysis of RNA from mouse tissues, using the mouse Vn cDNA as a hybridization probe, revealed the presence of a single transcript of 1.7 kilobases in mouse liver. Vn mRNA was not detectable in heart, lung, kidney, spleen, muscle, brain, thymus, testes, uterus, skin, adipose tissue, and aorta. The cellular localization of liver Vn mRNA was studied by in situ hybridization. Strong staining was observed only in hepatocytes, suggesting that these cells are the primary source of Vn in vivo.

Elevated plasma levels of type 1 plasminogen activator inhibitor (PAI- 1) have been implicated in mediating the fibrin deposition and occlusive lesions that occur within the placental vasculature in preeclampsia (PE) and intrauterine growth retardation (IUGR). In this report we identify the cells within the normal-appearing villous tissue that are responsible for the local production of PAI-1 in women with PE and IUGR. Levels for another fibrinolytic inhibitor (ie, type 2 plasminogen activator inhibitor [PAI-2]) were determined for comparative purposes. Elevated levels of PAI-1 were detected in placenta extracts from PE/IUGR patients (121 +/- 38 ng/mg, n = 8) when compared with the levels in placenta extracts from normal women (43 +/- 17 ng/mg, n = 10) or women with IUGR but not PE (51 +/- 22 ng/mg, n = 11). Immunohistochemical analysis of paraffin sections showed an increased immunoreactivity for PAI-1 in the placental villous syncytiotrophoblasts from PE/IUGR women compared with the immunostaining of placental samples from the normal or IUGR group. In contrast, antigen levels and immunostaining for PAI-2 were reduced in the placentas harvested from not only the PE/IUGR women (209 +/- 144 ng/mg) but also the IUGR group (169 +/- 106 ng/mg) in comparison with the PAI-2 levels in normal placentas (535 +/- 98 ng/mg). To document that the increased immunoreactivity for PAI-1 in PE/IUGR syncytiotrophoblasts was mediated by an increased production of PAI-1 within these cells, in situ hybridization analysis was performed. A strong positive signal for PAI-1 mRNA in villous syncytiotrophoblasts from PE patients (n = 5) was obtained after 2 weeks of exposure to the NTB2 emulsion in comparison with the weak signal for PAI-1 mRNA that required a 10-week exposure of the normal placenta sections (n = 10). Northern blotting for PAI-1 mRNA showed that both transcripts (ie, 3.2 and 2.3 kb) were elevated in samples of two PE patients in comparison with the PAI-1 mRNA transcripts present in a normal placenta and an IUGR placental sample. These results show increased PAI-1 and mRNA levels in placentas from PE patients and raise the possibility that localized elevated levels of PAI-1 may play a role in the initiation of placental damage, as well as in the thrombotic complications associated with this disease.

Plasminogen activator inhibitor 1 (PAI-1) is a rapid and spe-atherosclerotic human arteries (5: see below) and myocardial cific inhibitor of both tissue-type and urokinase-type plasinfarction (121, two disorders characterized by life-threaten