l -Tryptophan–Induced Vasodilation Is Enhanced in Preeclampsia
| Autor: | Theo Klein, Irwin Reiss, Emilie Hitzerd, Sam Schoenmakers, Daphne Merkus, Peter Sedlmayr, A.H. Jan Danser, Yolanda B. de Rijke, Michelle Broekhuizen |
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| Přispěvatelé: | Cardiology, Internal Medicine, Pediatrics, Clinical Chemistry, Obstetrics & Gynecology |
| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine medicine.medical_specialty Kynurenine pathway Placenta Vasodilation Nitric Oxide Preeclampsia Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pre-Eclampsia Downregulation and upregulation Pregnancy Internal medicine Internal Medicine medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase RNA Messenger Amino acid transporter Maternal-Fetal Exchange Kynurenine 030219 obstetrics & reproductive medicine Chemistry Tryptophan Arteries medicine.disease 030104 developmental biology medicine.anatomical_structure Endocrinology Fetal circulation 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Enzyme Induction Cytokines Female Nitric Oxide Synthase Carrier Proteins |
| Zdroj: | Hypertension, 76(1), 184-194. Lippincott Williams & Wilkins |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.120.14970 |
| Popis: | l -tryptophan induces IDO (indoleamine 2,3-dioxygenase) 1–dependent vasodilation. IDO1 is expressed in placental endothelial cells and downregulated in preeclampsia. Hypothesizing that this may contribute to diminished placental perfusion, we studied l -tryptophan–induced vasodilation in healthy and early-onset preeclampsia placental arteries, focusing on placental kynurenine pathway alterations. Despite IDO1 downregulation, kynurenine pathway metabolite concentrations (measured with ultra-performance liquid chromatography-tandem mass spectrometry) were unaltered in preeclamptic versus healthy placentas. Most likely, this is due to enhanced l -tryptophan uptake, evidenced by increased l -tryptophan levels in preeclamptic placentas. Ex vivo perfused cotyledons from healthy and preeclamptic placentas released similar amounts of l -tryptophan and kynurenine pathway metabolites into the circulations. This release was not altered by adding l -tryptophan in the maternal circulation, suggesting that l -tryptophan metabolites act intracellularly. Maternally applied l -tryptophan did appear in the fetal circulation, confirming placental passage of this essential amino acid. After in vitro incubation of placental arteries with IDO1-upregulating cytokines interferon-γ and tumor necrosis factor-α, l -tryptophan induced vasodilation. This vasodilation was attenuated by both IDO1 and nitric oxide (NO) synthase inhibitors. Despite IDO1 downregulation, l -tryptophan–induced relaxation was enhanced in preeclamptic versus healthy placental arteries. However, cytokine stimulation additionally upregulated the LAT ( l -type amino acid transporter) 1 in preeclamptic placental arteries only. Vasodilation to the lipophilic, transporter independent ethyl ester of l -tryptophan was reduced in preeclamptic versus healthy placental arteries, in agreement with reduced IDO1 expression. In conclusion, l -tryptophan induces IDO1- and NO-dependent relaxation in placental arteries, which is determined by l -tryptophan uptake rather than IDO1 expression. Increased l -tryptophan uptake might compensate for reduced IDO1 expression in preeclamptic placentas. |
| Databáze: | OpenAIRE |
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