title: The role of caveolae in endothelial cell dysfunction with a focus on nutrition and environmental toxicants.
abstract: Complications of vascular diseases, including atherosclerosis, are the number one cause of death in Western societies. Dysfunction of endothelial cells is a critical underlying cause of the pathology of atherosclerosis. Lipid rafts, and especially caveolae, are enriched in endothelial cells, and down-regulation of the caveolin-1 gene may provide protection against the development of atherosclerosis. There is substantial evidence that exposure to environmental pollution is linked to cardiovascular mortality, and that persistent organic pollutants can markedly contribute to endothelial cell dysfunction and an increase in vascular inflammation. Nutrition can modulate the toxicity of environmental pollutants, and evidence suggests that these affect health and disease outcome associated with chemical insults. Because caveolae can provide a regulatory platform for pro-inflammatory signalling associated with vascular diseases such as atherosclerosis, we suggest a link between atherogenic risk and functional changes of caveolae by environmental factors such as dietary lipids and organic pollutants. For example, we have evidence that endothelial caveolae play a role in uptake of persistent organic pollutants, an event associated with subsequent production of inflammatory mediators. Functional properties of caveolae can be modulated by nutrition, such as dietary lipids (e.g. fatty acids) and plant-derived polyphenols (e.g. flavonoids), which change activation of caveolae-associated signalling proteins. The following review will focus on caveolae providing a platform for pro-inflammatory signalling, and the role of caveolae in endothelial cell functional changes associated with environmental mediators such as nutrients and toxicants, which are known to modulate the pathology of vascular diseases.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Majkova
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hennig
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004785:Environmental Pollutants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D051379:Mice; D052756:Nutritional Sciences; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D015398:Signal Transduction
chemical_list: D051242:Caveolin 1; D004041:Dietary Fats; D004785:Environmental Pollutants; D005419:Flavonoids; D011084:Polycyclic Aromatic Hydrocarbons; D011078:Polychlorinated Biphenyls
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