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Functional evidences of fetal endothelial dysfunction as a programmed phenomenon in pregnancy diseases
Author(s) -
Sobrevia Luis,
Casanello Paola
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.403.4
Subject(s) - adenosine , umbilical vein , endocrinology , medicine , enos , endothelial dysfunction , placenta , fetus , nitric oxide , biology , chemistry , nitric oxide synthase , biochemistry , pregnancy , in vitro , genetics
Human endothelial dysfunction is a common feature in diseases of pregnancy such as gestational diabetes (GD), pre‐eclampsia (PE) and intrauterine growth restriction (IUGR). Metabolic changes include altered synthesis of nitric oxide (NO), and altered membrane transport of L‐arginine and adenosine in primary cultures of human umbilical vein (HUVEC, macrovascular) and placenta microvillous (hPMEC, microvascular) endothelial cells. These alterations are associated with modifications in the expression and activity of endothelial (eNOS) and inducible (iNOS) NO synthases, respectively, an effect maintained up to passage 5 in culture. Expression and activity of the human cationic amino acid transporter 1 (hCAT‐1) and equilibrative nucleoside transporters 1 (hENT1) and hENT2, as well as the corresponding SLC7A1 , SLC29A1 and SLC29A2 gene promoter activities, is exhibited by these cell types. Altered gene expression results from increased NO level, PKC, MAPK, hCHOP‐C/EBPα and Sp1 transcription factors activation. Reduced ENTs‐mediated adenosine transport in GD and PE is associated with stimulation of L‐arginine/NO pathway. In addition, hENT2 activity seems to intend to restore the reduced adenosine transport in GD and PE. It is suggested that a common functional characteristic leading to changes in the bioavailability of adenosine is evidenced by human fetal micro and macrovascular endothelium in GD, PE and IUGR. Supported by FONDECYT 1070865/1080534 (Chile).