The Renin-Angiotensin System Is Involved in the Production of Plasminogen Activator Inhibitor Type 1 by Cultured Endothelial Cells in Response to Chylomicron Remnants
| Autor: | Takeshi Tsujino, Takahiro Okumura, Mitsumasa Ohyanagi, Hiroshi Hosoai, Shinji Morimoto, Miho Masai, Yoshio Fujioka, Tadaaki Iwasaki, Tsuyoshi Sakoda |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Physiology Lipoproteins Blotting Western Electrophoretic Mobility Shift Assay Biology Rats Sprague-Dawley Renin-Angiotensin System Chylomicron remnant Internal medicine Chylomicrons Plasminogen Activator Inhibitor 1 Renin–angiotensin system Internal Medicine medicine Animals Phosphorylation education Cells Cultured Temocaprilat Mitogen-Activated Protein Kinase 1 education.field_of_study Angiotensin II receptor type 1 L-Lactate Dehydrogenase digestive oral and skin physiology Endothelial Cells Blotting Northern Angiotensin II Angiotensin II receptor type 2 Rats Endocrinology Human umbilical vein endothelial cell Cardiology and Cardiovascular Medicine Chylomicron |
| Zdroj: | Hypertension Research. 26:315-323 |
| ISSN: | 1348-4214 0916-9636 |
| Popis: | Triglyceride-rich lipoproteins have been suggested to promote atherosclerosis. Plasminogen activator inhibitor type 1 (PAI-1) plays an important role in the events of cardiovascular pathophysiology. The renin-angiotensin system influences various vascular functions, including PAI-1 production. We examined whether or not chylomicron remnants increased PAI-1 mRNA and protein production in endothelial cells and whether or not an inhibition of the renin-angiotensin system interfered with this effect. Chylomicron remnants were isolated from functionally hepatectomized rats injected with chylomicrons. Human umbilical vein endothelial cell cultures (HUVECs) were incubated with chylomicron remnants with or without an angiotensin-converting enzyme inhibitor (temocaprilat), an angiotensin II receptor type 1 antagonist (RNH-6270), or an angiotensin II receptor type 2 antagonist (PD123319). Chylomicron remnants increased PAI-1 secretion in HUVECs (0.5 microg/ml; 128.3 +/- 6.1%, the mean +/- SEM) as well as angiotensin II (10 nmol/l; 130.7 +/- 9.5%) in 18 h, as compared with the controls, as well as stimulated PAI-1 mRNA expression to a maximum level at 4 h. Temocaprilat and RNH-6270, but not PD123319, attenuated all of these effects. Chylomicron remnants enhanced nuclear extract binding to a very low-density lipoprotein response element in the PAI-1 promoter region and activated nuclear factor-kappaB. Extracellular signal-regulated kinase (ERK 1/2) was phosphorylated in response to chylomicron remnants. These effects were inhibited by temocaprilat or RNH-6270. In conclusion, chylomicron remnants increased protein secretion and mRNA expression of PAI-1 in HUVECs. Inhibition of the renin-angiotensin system reduced this stimulation. |
| Databáze: | OpenAIRE |
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