The fact that PAI1 levels and angiogenesis in turn are associated with hypoxia in placental insufficiency, and not its molecular angiogenic regulators VEGF and FGF-2, indicates upregulation may be largely through HIF-1 mediated mechanisms.
Nevertheless, investigations of the expression of PAI1 should account for cortisone administration as a potential confounder to a marker in severe preterm pregnancies.
Among the most important genes up-regulated in ECs in this condition (36) are those that denote EC activation, (45) namely, IL-8, MCP1, VCAM1, PAI1
, Gro-[alpha], and E-selectin.
The primer 5'-AGCCAGACAAGGTTGTTGACAC-3' (nucleotides -741 to -720, relative to the transcription start site) and the primer 5'-CAGAGGACTCTTGGTTTTCCC-3' (nucleotides -628 to -607, relative to the transcription start site) were used to amplify, respectively, a 134- or a 135-bp fragment of the human PAI1 gene that harbors the polymorphic site 675 nucleotides upstream from the start of transcription (GenBank locus HSPAI11) (17).
The growing evidence that the PAI-1 concentrations in the circulation are related to the common 4G/5G polymorphism in the promoter of the PAI1 gene has opened the possibility of using PAI1 genotype as a marker for life-long exposure to differing PAI-1 concentrations.