title: Northern contaminant mixtures induced morphological and functional changes in human coronary artery endothelial cells under culture conditions typifying high fat/sugar diet and ethanol exposure.
abstract: It has been reported that Northern populations are exposed to mixtures of various environmental contaminants unique to the Arctic (Northern contaminant mixtures - NCM) at a large range of concentrations, depending on their geological location, age, lifestyle and dietary habits. To determine if these contaminants may contribute to a cardiovascular health risk, especially when combined with a high fat and sugar diet and ethanol exposure, we treated human coronary artery endothelial cells (HCAEC) with two mixtures of 4 organic (NCM1) or 22 organic and inorganic (NCM2) chemicals detected in Northerners' blood during 2004-2005 in the presence or absence of low-density lipoprotein (1.5mg/ml), very-low-density lipoprotein (1.0mg/ml) and glucose (10mmol/L) (LVG), and in the absence or presence of 0.1% ethanol. After 24h of exposure, cell morphology and markers of cytotoxicity and endothelial function were examined. NCM1 treatment did not affect cell viability, but increased cell size, disrupted cell membrane integrity, and decreased cell density, uptake of small peptides, release of endothelin-1 (ET-1) and plasminogen activator inhibitor (PAI), while causing no changes in endothelial nitric oxide synthase (eNOS) protein expression and nitric oxide (NO) release. In contrast, NCM2 decreased cell viability, total protein yield, uptake of small peptides, eNOS protein expression, and NO release and caused membrane damage, but caused no changes in the secretion of ET-1, prostacyclin and PAI. The presence of LVG and/or alcohol did or did not influence the effects of NCM1 or NCM2 depending on the endpoint and the mixture examined. These results suggested that the effects of one or one group of contaminants may be altered by the presence of other contaminants, and that with or without the interaction of high fat and sugar diet and/or ethanol exposure, NCMs at the concentrations used caused endothelial dysfunction in vitro. It remains to be investigated if these effects of NCMs also occur in vivo.
authors: Toxicology Research Division, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada K1A 0K9; Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1S 5B6.
authors: Maria
authors: M
authors: Florian
authors: Jin
authors: J
authors: Yan
authors: Saad
authors: S
authors: Ulhaq
authors: Melanie
authors: M
authors: Coughlan
authors: Mahemuti
authors: M
authors: Laziyan
authors: William
authors: W
authors: Willmore
authors: Xiaolei
authors: X
authors: Jin
mesh_terms: D001110:Arctic Regions; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045424:Complex Mixtures / Q000097:blood / Q000633:toxicity*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008954:Models, Biological
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D045424:Complex Mixtures; D019422:Dietary Sucrose; D004785:Environmental Pollutants; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D000431:Ethanol
keywords: Cardiovascular disease; Ethanol exposure; High fat and sugar diet; Human coronary artery endothelial cells; Northern contaminant mixtures