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

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 whic...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2018-11-01
Series:Translational Medicine Communications
Subjects:
Online Access:http://link.springer.com/article/10.1186/s41231-018-0029-9
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author 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
author_facet 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
author_sort Ronodeep Mitra
collection DOAJ
description 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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spelling doaj.art-36a6d30b86254938a457135e3850f4352022-12-22T01:19:48ZengBMCTranslational Medicine Communications2396-832X2018-11-013111510.1186/s41231-018-0029-9The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammationRonodeep Mitra0Ju Qiao1Sudharsan Madhavan2Gerard L. O’Neil3Bailey Ritchie4Praveen Kulkarni5Srinivas Sridhar6Anne L. van de Ven7Erica M. Cherry Kemmerling8Craig Ferris9James A. Hamilton10Eno E. Ebong11Department of Bioengineering, College of Engineering, Northeastern UniversityDepartment of Mechanical and Industrial Engineering, College of Engineering, Northeastern UniversityDepartment of Mechanical Engineering, College of Engineering, Tufts UniversityDepartment of Biology, College of Science, Northeastern UniversityDepartment of Chemical Engineering, College of Engineering, Northeastern UniversityDepartment of Psychology, College of Science, Northeastern UniversityDepartment of Bioengineering, College of Engineering, Northeastern UniversityDepartment of Physics, College of Science, Northeastern UniversityDepartment of Mechanical Engineering, College of Engineering, Tufts UniversityDepartment of Psychology, College of Science, Northeastern UniversityDepartment of Physiology and Biophysics, Boston University School of MedicineDepartment of Bioengineering, College of Engineering, Northeastern UniversityAbstract 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.http://link.springer.com/article/10.1186/s41231-018-0029-9GlycocalyxEndothelial dysfunctionAtherogenesisInflammationHigh fat dietDisturbed blood flow
spellingShingle 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
The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation
Translational Medicine Communications
Glycocalyx
Endothelial dysfunction
Atherogenesis
Inflammation
High fat diet
Disturbed blood flow
title The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation
title_full The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation
title_fullStr The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation
title_full_unstemmed The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation
title_short The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation
title_sort comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation
topic Glycocalyx
Endothelial dysfunction
Atherogenesis
Inflammation
High fat diet
Disturbed blood flow
url http://link.springer.com/article/10.1186/s41231-018-0029-9
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