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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Retinoic acid induces PGI synthase expression in human endothelial cells
Mercedes Camacho1, Cristina Rodríguez, Juliana Salazar
1Angiology, Vascular Biology, and Inflammation Laboratory of the Institute of Research, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
Journal of Lipid Research
|May 7, 2008
Summary
Retinoic acid (RA) enhances prostaglandin I(2) production in endothelial cells by increasing prostaglandin I(2) synthase (PGIS) expression via retinoic acid receptors (RARs). This suggests RA may benefit cardiovascular health.
Area of Science:
- Endocrinology
- Molecular Biology
- Cardiovascular Research
Background:
- Retinoic acid (RA) possesses anti-inflammatory, anti-tumor, and immunomodulatory properties.
- Arachidonic acid (AA) metabolites play critical roles in inflammation, thrombosis, and angiogenesis.
- Human umbilical vein endothelial cells (HUVECs) are central to vascular function and hemostasis.
Purpose of the Study:
- To investigate the impact of retinoic acid (RA) on arachidonic acid (AA) metabolism in HUVECs.
- To elucidate the molecular mechanisms underlying RA's effects on prostaglandin I(2) (PGI(2)) production.
- To assess the potential cardiovascular benefits of RA.
Main Methods:
- Enzyme-immunoassay to measure 6-oxo-PGF(1alpha) levels.
- Immunoblotting for cyclooxygenase-isoenzyme expression.
- Real-time PCR and Western blotting for prostaglandin I(2) synthase (PGIS) mRNA and protein.
- HPLC analysis of eicosanoids from labeled AA.
- Transient transfection assays for PGIS transcriptional activity.
- Use of retinoic acid receptor (RAR) and retinoid X receptor (RXR) antagonists, actinomycin D, and cycloheximide.
Main Results:
- 13-cis-RA significantly increased spontaneous and thrombin-induced PGI(2) release in HUVECs.
- RA enhanced HUVECs' ability to inhibit AA-induced platelet aggregation.
- RA upregulated PGIS activity and expression (mRNA and protein) without affecting cyclooxygenase expression or activity.
- The RA-induced PGIS upregulation was mediated by RAR and involved transcriptional activation.
- Inhibition of PGIS expression by actinomycin D and cycloheximide confirmed the involvement of new gene transcription and protein synthesis.
Conclusions:
- Retinoic acid (RA) modulates arachidonic acid metabolism in endothelial cells primarily by upregulating prostaglandin I(2) synthase (PGIS) expression through retinoic acid receptors (RARs).
- These findings support the potential therapeutic role of RA in managing cardiovascular risks by enhancing protective PGI(2) production.
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