title: Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells.
abstract: Obesity and type 2 diabetes lead to dramatically increased risks of atherosclerosis and CHD. Multiple mechanisms converge to promote atherosclerosis by increasing endothelial oxidative stress and up-regulating expression of pro-inflammatory molecules. Microvesicles (MV) are small ( < 1 μm) circulating particles that transport proteins and genetic material, through which they are able to mediate cell-cell communication and influence gene expression. Since MV are increased in plasma of obese, insulin-resistant and diabetic individuals, who often exhibit chronic vascular inflammation, and long-term feeding of a high-fat diet (HFD) to rats is a well-described model of obesity and insulin resistance, we hypothesised that this may be a useful model to study the impact of MV on endothelial inflammation. The number and cellular origin of MV from HFD-fed obese rats were characterised by flow cytometry. Total MV were significantly increased after feeding HFD compared to feeding chow (P< 0·001), with significantly elevated numbers of MV derived from leucocyte, endothelial and platelet compartments (P< 0·01 for each cell type). MV were isolated from plasma and their ability to induce reactive oxygen species (ROS) formation and vascular cell adhesion molecule (VCAM)-1 expression was measured in primary rat cardiac endothelial cells in vitro. MV from HFD-fed rats induced significant ROS (P< 0·001) and VCAM-1 expression (P= 0·0275), indicative of a pro-inflammatory MV phenotype in this model of obesity. These findings confirm that this is a useful model to further study the mechanisms by which diet can influence MV release and subsequent effects on cardio-metabolic health.
authors.affiliation: Department of Comparative Biomedical Sciences,Royal Veterinary College,Royal College Street,LondonNW1 0TU,UK.
authors.forename: L F
authors.initials: LF
authors.lastname: Heinrich
authors.affiliation: Department of Comparative Biomedical Sciences,Royal Veterinary College,Royal College Street,LondonNW1 0TU,UK.
authors.forename: D K
authors.initials: DK
authors.lastname: Andersen
authors.affiliation: Department of Comparative Biomedical Sciences,Royal Veterinary College,Royal College Street,LondonNW1 0TU,UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Cleasby
authors.affiliation: Department of Comparative Biomedical Sciences,Royal Veterinary College,Royal College Street,LondonNW1 0TU,UK.
authors.forename: C
authors.initials: C
authors.lastname: Lawson
mesh_terms: D000818:Animals; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007333:Insulin Resistance; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1
keywords: Endothelium; Extracellular vesicles; Inflammation; Microvesicles; Obesity; Oxidative stress; Vascular cell adhesion molecule-1