Abstract
The primary role of cigarette smoking in the development of coronary heart disease is to cause damage to the vascular endothelium, leading to endothelial cell dysfunction and initiating the pathogenesis of coronary atherosclerosis. We studied the response of human coronary artery endothelial cells to nicotine exposure by examining the expression of a panel of genes encoding molecules that have been shown to be involved in atherogenesis. Treatment of primary human coronary artery endothelial cells with nicotine for 24 h at concentrations (10(-5) and 10(-7) M) similar to those in the blood of smokers resulted in increased mRNA levels of endothelial nitric oxide synthase, angiotensin-I converting enzyme, tissue-type plasminogen activator, plasminogen activator inhibitor-1, von Willebrand factor, and vascular cell adhesion molecule-1. No change was detected in the expression levels of the genes encoding basic fibroblast growth factor, endothelin-1, endothelial leukocyte adhesion molecule-1 and matrix metalloproteinase-2 under these conditions. These data indicate that nicotine alters the expression of a number of endothelial genes whose products play major roles in regulating the vascular tone and thrombogenicity, making a contribution to the understanding of the effects of cigarette smoking on the development of coronary atherosclerosis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Biomarkers
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cells, Cultured
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Coronary Artery Disease / chemically induced*
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Coronary Artery Disease / metabolism
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Coronary Artery Disease / pathology
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Coronary Vessels / drug effects*
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Coronary Vessels / pathology
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DNA Primers / chemistry
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism*
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Endothelium, Vascular / pathology
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Gene Expression / drug effects*
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Humans
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Nicotine / adverse effects*
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Nicotinic Agonists / adverse effects*
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Peptidyl-Dipeptidase A / genetics
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Peptidyl-Dipeptidase A / metabolism
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Plasminogen Activator Inhibitor 1 / genetics
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Plasminogen Activator Inhibitor 1 / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Tissue Plasminogen Activator / genetics
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Tissue Plasminogen Activator / metabolism
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Ubiquitin-Protein Ligases
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / metabolism
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von Willebrand Factor / genetics
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von Willebrand Factor / metabolism
Substances
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Biomarkers
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Carrier Proteins
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DNA Primers
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Nicotinic Agonists
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Plasminogen Activator Inhibitor 1
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RNA, Messenger
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Vascular Cell Adhesion Molecule-1
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von Willebrand Factor
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Nicotine
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NOSIP protein, human
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Ubiquitin-Protein Ligases
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Peptidyl-Dipeptidase A
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Tissue Plasminogen Activator