@article { , 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.}, doi = {10.1017/S0007114515001117}, issn = {0007-1145}, issue = {11}, journal = {BRITISH JOURNAL OF NUTRITION}, pages = {1704-11}, publicationstatus = {Published}, publisher = {Cambridge University Press}, url = {https://rvc-repository.worktribe.com/output/1401204}, volume = {113}, keyword = {ePrints migration}, year = {2015}, author = {Heinrich, L F and Andersen, D K and Cleasby, M E and Lawson, C} }