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.

Keywords: Cardiovascular disease; Ethanol exposure; High fat and sugar diet; Human coronary artery endothelial cells; Northern contaminant mixtures.