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

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
• Electronic ISSN: 1475-2662
• 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