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Oxidized low density lipoproteins stimulate phosphoinositide turnover in cultured vascular smooth muscle cells
- Source :
- Arteriosclerosis and Thrombosis: A Journal of Vascular Biology. 12:278-285
- Publication Year :
- 1992
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1992.
-
Abstract
- Atherogenesis is associated with alterations in the properties of different cell types, including monocytes/macrophages (foam cell formation), platelets (increased aggregation), endothelial cells (injury), and smooth muscle cells (SMCs) (lipid accumulation or foam cell formation). Oxidized low density lipoproteins (ox-LDL) play a key role in this vascular pathology. This study investigated the ability of ox-LDL to elicit chemical signaling events in cultured human vascular smooth muscle cells (VSMCs). Ox-LDL was found to stimulate phospholipase C-mediated phosphoinositide turnover in human VSMCs. This response occurred rapidly (within 1 minute) and at low concentrations of ox-LDL (half-maximal effective concentration, approximately 5 micrograms/ml). Ox-LDL-stimulated inositol phosphate accumulation in human VSMCs was inhibited by pretreatment of cells with phorbol 12-myristate 13-acetate and with compounds that elevate cyclic AMP or cyclic GMP. Ca2+ antagonists also blocked the effects of ox-LDL on phosphoinositide turnover. Inhibitors of receptor-endocytotic processes (including receptor clustering, cross-linking, and cytoskeleton-dependent internalization) effectively prevented ox-LDL-induced inositol phosphate generation. The data suggest that ox-LDL promotes phospholipase C-mediated phosphoinositide turnover in a manner analogous to that for other Ca(2+)-mobilizing hormones. The results also support an association between phosphoinositide turnover and receptor-mediated endocytosis. Prevention of the direct effects of ox-LDL on SMCs could prove an interesting therapeutic avenue for the prevention of atherosclerosis.
- Subjects :
- medicine.medical_specialty
Vascular smooth muscle
Phospholipase
Biology
Phosphatidylinositols
Endocytosis
Second Messenger Systems
Muscle, Smooth, Vascular
chemistry.chemical_compound
Internal medicine
Cyclic AMP
medicine
Humans
Inositol phosphate
Cyclic GMP
Cells, Cultured
Foam cell
chemistry.chemical_classification
Calcium Channel Blockers
Lipoproteins, LDL
Endocrinology
chemistry
Type C Phospholipases
Second messenger system
Phorbol
Tetradecanoylphorbol Acetate
lipids (amino acids, peptides, and proteins)
Receptor clustering
Cardiology and Cardiovascular Medicine
Oxidation-Reduction
Subjects
Details
- ISSN :
- 10498834
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Accession number :
- edsair.doi.dedup.....18832096986376fea2f6658b6abff62b