Translational Medicine Communications (Nov 2018)

The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation

  • Ronodeep Mitra,
  • Ju Qiao,
  • Sudharsan Madhavan,
  • Gerard L. O’Neil,
  • Bailey Ritchie,
  • Praveen Kulkarni,
  • Srinivas Sridhar,
  • Anne L. van de Ven,
  • Erica M. Cherry Kemmerling,
  • Craig Ferris,
  • James A. Hamilton,
  • Eno E. Ebong

DOI
https://doi.org/10.1186/s41231-018-0029-9
Journal volume & issue
Vol. 3, no. 1
pp. 1 – 15

Abstract

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Abstract Background and aims Endothelial surface glycocalyx shedding plays a role in endothelial dysfunction and increases vessel wall permeability, which can lead to inflammation and atherogenesis. We sought to elucidate whether a high fat diet (HFD) or disturbed blood flow conditions, both of which are atherogenic risk factors, would contribute more detrimentally to pre-atherosclerotic loss of endothelial glycocalyx integrity and vascular inflammation. Methods Six to seven week-old C57BL/6-background apolipoprotein-E-knockout (ApoE-KO) male mice were either fed a chow diet, fed a modified Western HFD, and/or subjected to a partial left carotid artery (LCA) ligation procedure to induce disturbed blood flow patterns in the LCA. Mice were sacrificed after 1 week of experimental conditions. Both LCA and right carotid artery (RCA) vessels were dissected and preserved to compare glycocalyx coverage and thickness as well as macrophage accumulation in carotid arterial walls amongst and between cohorts. Results Glycocalyx coverage of the endothelium was significantly reduced in the LCAs of HFD fed mice when compared to the control. More significant reduction in glycocalyx coverage occurred in the LCAs of mice exposed to disturbed flow by partial LCA ligation when compared to the control. No differences were found in glycocalyx coverage of RCAs from all cohorts. Regarding inflammation, no difference in macrophage accumulation in carotid arterial walls was observed when comparing the LCAs and RCAs of control and HFD fed mice. However, macrophage infiltration in vessel walls showed a 20-fold increase in the LCAs exposed to disturbed flow following ligation, when compared to control LCAs, while no such statistical difference was observed between the RCAs of the group. Conclusions In our mouse model, endothelial glycocalyx integrity was compromised more by disturbed blood flow patterns than by exposure of the carotid vessel to HFD conditions. The pathophysiological implications include endothelial dysfunction, which correlates to macrophage infiltration in vessel walls and promotes atherogenesis.

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