Summary
Under normal physiologic conditions, tissue factor pathway inhibitor (TFPI) is synthesized
primarily by the microvascular endothelium. Using Northern blotting, we studied its
transcriptional expression in different organs and compared it with the expression
of two other endothelial specific proteins, namely thrombomodulin (TM) and von Willebrand
factor (vWF). The order of mRNA expression for each protein was: TFPI–placenta>lung>liver>kidney>heart>skeletal
muscle≥pancreas>brain; TM–heart>pancreas>lung>skeletal muscle>kidney≥liver>placenta>brain;
and vWF–heart>skeletal muscle>pancreas>lung≥kidney>placenta>brain>liver. Notably,
heart expressed TM and vWF mRNA in large amounts and only small amounts of TFPI whereas
lung expressed all three mRNAs in significant amounts. Placenta, on the contrary,
expressed large amounts of TFPI but only small amounts of TM and vWF mRNAs. Brain
by this technique was found to express undetectable amounts of TFPI and TM mRNAs but
small amounts of vWF mRNA. The expression of TFPI mRNA in the brain was however detected
by RT/PCR and the antigen was localized to the endothelium of microvessels as well
as to the astrocytes and oligodendrocytes. Since ultimate expression of proteins is
linked to the expression of their mRNAs, our data support a concept that vascular
endothelium is made up of phenotypically diverse groups of cells and that endothelial
cells of different vascular beds express specific sets of genes that enable them to
carry out tissue-specific functions. Importantly, since astrocytes are known to express
tissue factor, the TFPI expression by these cells may control coagulation in their
microenvironment and their response to injury and inflammation.