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Human fibroblasts downregulate plasminogen activator inhibitor type-1 in
cultured human macrovascular and microvascular endothelial cells
JC Zhang, A Fabry, L Paucz, J Wojta and BR Binder
Department of Vascular Biology and Thrombosis Research, University of
Vienna, Austria.
We have previously reported that plasminogen activator inhibitor type-1
(PAI-1) expression in endothelial cells (ECs) can be modulated differently
by smooth muscle cells depending on their origin. Human pulmonary artery
smooth muscle cells (HPASMCs) strongly downregulated PAI-1 expression in
ECs. Fibroblasts (FBs) are another cell type that could come in close
contact with ECs. Therefore, it was the aim of this study to investigate
whether FBs could also influence the fibrinolytic potential of ECs. As in
the case of HPASMCs, PAI-1 antigen produced by human umbilical vein ECs
(HUVECs) cocultured with human skin FBs (HSFBs) was significantly lower as
compared with the sum of PAI-1 secreted by the respective cell types
cultured separately. Not only HUVECs but also human skin microvascular ECs
(HSMECs) responded in a dose-dependent way to serum-free conditioned media
(CM) from HSFBs from one individual donor. Similar results were obtained
when CM from HSFBs from four other individual donors were used. PAI-1 mRNA
decreased in HUVECs incubated for 6 hours with HSFB-CM to 24% to 55% of
control, depending on the preparation of HSFBs used. A significant PAI-1
downregulatory effect was only observed when CM from low-passage HSFBs (up
to passage no. 5) was used, whereas no reduction in EC PAI-1 production was
observed with CM obtained from HSFBs in passage no. 8. This PAI-1
downregulatory activity present in HSFB-CM was heat-labile and had a
molecular mass of approximately 5 kD. When CM from HPASMCs was analyzed in
the same way, an almost identical elution profile was found. In conclusion,
our data showed that FBs can decrease the expression of PAI-1 in ECs. Such
an effect could be operative during wound-healing and at other capillary
sites where FBs could render ECs profibrinolytic, thereby facilitating
processes requiring an increase in proteolytic activity such as EC
migration and proliferation.
Volume 88,
Issue 10,
pp. 3880-3886,
11/15/1996
Copyright © 1996 by The American Society of Hematology

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