Abstract
Objective:
Elevated plasma levels of endothelial microparticles (EMPs) are associated with the presence of clinical atherosclerosis. Considering the anti-inflammatory properties of HMG-CoA reductase inhibitors on the endothelium, we studied the effect of fluvastatin on the release of EMPs in cultured human coronary artery endothelial cells (HCAEC).
Methods and results:
EMPs were generated in TNF-alpha-activated HCAECs. The absolute number of EMPs was enumerated using a novel two-color flow cytometric immunostaining technique with TruCount beads as an internal reference. EMPs are defined as EC membrane vesicles (1-2 microm in size) with a characteristic immunophenotype. The addition of fluvastatin to TNF-alpha-activated HCAECs significantly suppressed EMP release. Fluvastatin suppressed TNF-alpha-induced Rho activation. The Rho-kinase inhibitor, Y-27632, reproduced the effect of statin.
Conclusion:
EMP release from TNF-alpha-activated HCAECs is suppressed by fluvastatin. In addition, the Rho/Rho-kinase may play an important role in modulating EMP release.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antigens, CD
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Arteries / drug effects
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Arteries / metabolism
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Cells, Cultured
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Coronary Vessels / drug effects
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Coronary Vessels / metabolism
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Endoglin
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism*
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Enzyme Activation / drug effects
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Fatty Acids, Monounsaturated / pharmacology*
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Fluvastatin
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Humans
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Indoles / pharmacology*
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Integrin alphaV / metabolism
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins / blood*
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Membrane Glycoproteins / drug effects*
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Membrane Glycoproteins / immunology
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Particle Size
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Protein Serine-Threonine Kinases / metabolism*
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Receptors, Cell Surface
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Tumor Necrosis Factor-alpha / pharmacology*
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Vascular Cell Adhesion Molecule-1 / metabolism
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rho-Associated Kinases
Substances
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Antigens, CD
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ENG protein, human
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Endoglin
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Fatty Acids, Monounsaturated
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Indoles
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Integrin alphaV
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Receptors, Cell Surface
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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Fluvastatin
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Protein Serine-Threonine Kinases
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rho-Associated Kinases