Human endothelial progenitors constitute targets for environmental atherogenic polycyclic aromatic hydrocarbons.
Cigarette smoking, a well-known cardiovascular risk factor, has been recently demonstrated to decrease circulating endothelial progenitor cell (EPC) number. Owing to the fact that polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) constitute major components of tobacco smoke, the present study was designed to analyze the effects of these chemicals on the development of human EPC cultures from peripheral blood mononuclear cells. Treatment by BP markedly impaired EPC number and EPC colonies in a dose-dependent manner. Such deleterious effects were abrogated using 3'-methoxy-4'-nitroflavone, a pure antagonist of the aryl hydrocarbon receptor, highlighting the involvement of this receptor in PAH toxicity towards EPCs. Additional events such as cytochrome P-450-dependent PAH metabolism and formation of PAH-related adducts to cellular macromolecules were also required. Overall, these data established EPCs as new cellular targets of PAHs, which may contribute to the deleterious cardiovascular effects of environmental substances containing these chemicals, especially tobacco smoke.
van Grevenynghe
Julien
J
INSERM U620, Rennes, France.
Monteiro
Patricia
P
Gilot
David
D
Fest
Thierry
T
Fardel
Olivier
O
D050197:Atherosclerosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018680:Cholinergic Antagonists / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004785:Environmental Pollutants / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D011950:Receptors, Cholinergic / Q000378:metabolism
D018680:Cholinergic Antagonists; D004785:Environmental Pollutants; D011950:Receptors, Cholinergic; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1