Upregulation of prostacyclin synthesis-related gene expression by shear stress in vascular endothelial cells
| Autor: | Jun-ichi Kambayashi, Kazuhiro Okahara, Bing Sun |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Prostaglandin Vasodilation Prostacyclin 6-Ketoprostaglandin F1 alpha Biology Umbilical vein Phospholipases A chemistry.chemical_compound Downregulation and upregulation Cytochrome P-450 Enzyme System Internal medicine medicine Humans Cells Cultured Arachidonic Acid Membrane Proteins Epoprostenol Up-Regulation Endothelial stem cell Intramolecular Oxidoreductases Isoenzymes Phospholipases A2 Endocrinology chemistry Gene Expression Regulation Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Cyclooxygenase 1 lipids (amino acids peptides and proteins) Arachidonic acid Cyclooxygenase Endothelium Vascular Stress Mechanical Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 18(12) |
| ISSN: | 1079-5642 |
| Popis: | Abstract —Prostacyclin (prostaglandin I 2 , PGI 2 ) has a variety of functions, including inhibition of smooth muscle cell proliferation, vasodilation, and antiplatelet aggregation. PGI 2 production in endothelial cells has been reported to increase biphasically after shear loading, but the underlying mechanism is not well understood. To clarify the mechanism for the second phase of PGI 2 upregulation, we examined the gene expression of the enzymes involved in PGI 2 production in human umbilical vein endothelial cells (HUVECs) after shear-stress (24 dyne/cm 2 ) loading. The production of 6-keto-PGF 1α , a stable metabolite of PGI 2 , increased time-dependently under shear stress. The arachidonic acid liberation from membrane phospholipids in HUVECs after 12 hours of shear loading was increased significantly compared with the static condition. No change was observed for cytosolic phospholipase A 2 expression, as detected by reverse transcription–polymerase chain reaction and Western blotting. Cyclooxygenase (COX)-1 mRNA increased after 1 hour of shear loading, and the increase lasted for 12 hours, the longest time tested, whereas COX-2 mRNA increased after 1 hour of shear loading and peaked at 6 hours. An increase of COX-1 expression was detected at 12 hours of shear loading by Western blotting. No expression of COX-2 was detected in the static control, but induced expression was observed at 6 hours after shear loading. PGI 2 synthase was also found to be upregulated. These results suggest that the elevated PGI 2 production by shear stress is mediated by increased arachidonic acid release and a combination of increased expression of COXs and PGI 2 synthase. |
| Databáze: | OpenAIRE |
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