Abstract
The objective of this study was to investigate the gene expression signature of monocyte/macrophages and the pleiotropic effects of atorvastatin on monocytes in atherosclerotic patients. Forty patients with coronary heart diseases were randomly assigned to double-blind therapy with either 20 or 80 mg per day of atorvastatin. Follow-up visits occurred at weeks 6 and 12, including complete chemistry and lipid analyses and quantification of 14 target genes in monocytes. After 12 weeks of therapy, both groups gained beneficial alterations in lipid profiles. Both groups experienced significant reductions in gene expression of lipoprotein-associated phospholipase A2, CD13, leptin receptor, matrix metalloproteases-1, legumain, and prolyl oligopeptidase after 12 weeks of therapy. Only tumor protein 53 was increased in the atorvastatin 80-mg group. Moreover, nonsignificant interactions between dosage and duration of therapy were found. The pleiotropic effects of statins in atherosclerotic patients include increased expression of genes involved in apoptosis of monocyte/macrophage, inhibition of inflammatory responses, antioxidant properties, prevention of foam cell formation, and stabilization of atherosclerotic plaques. This property fuels potential clinical significance.
Publication types
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism
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Administration, Oral
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Anticholesteremic Agents / therapeutic use*
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Apoptosis / drug effects
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Atherosclerosis / complications
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Atherosclerosis / drug therapy*
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Atherosclerosis / metabolism*
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Atorvastatin
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CD13 Antigens / metabolism
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Coronary Disease / drug therapy
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Coronary Disease / etiology
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Coronary Disease / metabolism
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Cysteine Endopeptidases / metabolism
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Dose-Response Relationship, Drug
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Double-Blind Method
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Female
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Follow-Up Studies
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Gene Expression / drug effects
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Heptanoic Acids / metabolism
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Heptanoic Acids / therapeutic use*
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Humans
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Lipid Metabolism / drug effects
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Male
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Matrix Metalloproteinase 1 / metabolism
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Middle Aged
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Monocytes / drug effects
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Monocytes / metabolism*
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Prolyl Oligopeptidases
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Pyrroles / therapeutic use*
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Receptors, Leptin / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Serine Endopeptidases / metabolism
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Time Factors
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Treatment Outcome
Substances
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Anticholesteremic Agents
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Heptanoic Acids
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Pyrroles
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Receptors, Leptin
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Atorvastatin
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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CD13 Antigens
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Serine Endopeptidases
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PREPL protein, human
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Prolyl Oligopeptidases
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Cysteine Endopeptidases
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asparaginylendopeptidase
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Matrix Metalloproteinase 1