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Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells

Heinrich, L F; Andersen, D K; Cleasby, M E; Lawson, C

Authors

L F Heinrich

D K Andersen

M E Cleasby

C Lawson



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.

Citation

Heinrich, L. F., Andersen, D. K., Cleasby, M. E., & Lawson, C. (2015). Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells. British Journal of Nutrition, 113(11), 1704-11. https://doi.org/10.1017/S0007114515001117

Journal Article Type Article
Acceptance Date Mar 10, 2015
Publication Date Apr 16, 2015
Deposit Date Apr 30, 2015
Publicly Available Date Apr 30, 2015
Journal BRITISH JOURNAL OF NUTRITION
Print ISSN 0007-1145
Publisher Cambridge University Press
Peer Reviewed Peer Reviewed
Volume 113
Issue 11
Pages 1704-11
DOI https://doi.org/10.1017/S0007114515001117
Public URL https://rvc-repository.worktribe.com/output/1401204

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