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Cholesterol enrichment of arterial smooth muscle cells upregulates cytokine-induced nitric oxide synthesis.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1993 Feb 26; Vol. 191 (1), pp. 103-9. - Publication Year :
- 1993
-
Abstract
- Endothelium-derived relaxing factor/nitric oxide (EDRF/NO) is produced by the vascular wall and is a key modulator of vascular tone and blood pressure. NO is also produced by vascular smooth muscle (VSMC) where it can inhibit proliferation. Since cytokine-activated VSMC proliferation is a major event in the development of atherosclerosis, we investigated the influence of cholesterol (CE)-enrichment of VSMC on cytokine-induced NO synthesis. Treatment of VSMC with native LDL for one week did not promote CE-accretion or alter NO production following exposure to endotoxin (LPS). In contrast, CE-enrichment by cationized LDL augmented LPS-induction of NO synthesis 2-5-fold. While TNF-alpha promoted little NO synthesis in control VSMC, it was very potent after CE-enrichment. Similarly, CE-enrichment augmented IL-1 alpha-induced NO synthesis. However, CE-enrichment did not affect the synergistic induction of NO synthesis by cytokines in combination with IFN-gamma. Our findings suggest that CE-enrichment of VSMC upregulates signal transduction pathways which mediate cytokine and LPS induction of NO synthase activity.
- Subjects :
- Animals
Aorta, Thoracic drug effects
Cells, Cultured
Escherichia coli
Foam Cells physiology
Humans
Kinetics
Lipopolysaccharides pharmacology
Lipoproteins, LDL blood
Lipoproteins, LDL isolation & purification
Lipoproteins, LDL pharmacology
Muscle, Smooth, Vascular drug effects
Rats
Recombinant Proteins pharmacology
Tumor Necrosis Factor-alpha pharmacology
Aorta, Thoracic metabolism
Cholesterol pharmacology
Cytokines pharmacology
Interferon-gamma pharmacology
Muscle, Smooth, Vascular metabolism
Nitric Oxide metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 191
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 8447815
- Full Text :
- https://doi.org/10.1006/bbrc.1993.1190