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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BMC
2018-11-01
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Series: | Translational Medicine Communications |
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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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issn | 2396-832X |
language | English |
last_indexed | 2024-12-11T05:16:26Z |
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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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