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Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice

Optimal cell spreading and interplay of vascular smooth muscle cells (VSMC), inflammatory cells, and cell adhesion molecules (CAM) are critical for progressive atherosclerosis and cardiovascular complications. The role of vitronectin (VTN), a major cell attachment glycoprotein, in the pathogenesis o...

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Autores principales: Chakravarty, Devasmita, Ray, Aleepta Guha, Chander, Vivek, Mabalirajan, Ulaganathan, Mondal, Prakash Chandra, Siddiqui, Khawer N., Sinha, Bishnu Prasad, Konar, Aditya, Bandyopadhyay, Arun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814562/
https://www.ncbi.nlm.nih.gov/pubmed/35141476
http://dx.doi.org/10.1096/fba.2021-00108
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author Chakravarty, Devasmita
Ray, Aleepta Guha
Chander, Vivek
Mabalirajan, Ulaganathan
Mondal, Prakash Chandra
Siddiqui, Khawer N.
Sinha, Bishnu Prasad
Konar, Aditya
Bandyopadhyay, Arun
author_facet Chakravarty, Devasmita
Ray, Aleepta Guha
Chander, Vivek
Mabalirajan, Ulaganathan
Mondal, Prakash Chandra
Siddiqui, Khawer N.
Sinha, Bishnu Prasad
Konar, Aditya
Bandyopadhyay, Arun
author_sort Chakravarty, Devasmita
collection PubMed
description Optimal cell spreading and interplay of vascular smooth muscle cells (VSMC), inflammatory cells, and cell adhesion molecules (CAM) are critical for progressive atherosclerosis and cardiovascular complications. The role of vitronectin (VTN), a major cell attachment glycoprotein, in the pathogenesis of atherosclerosis remains elusive. In this study, we attempt to examine the pathological role of VTN in arterial plaque progression and inflammation. We found that, relative expression analysis of VTN from the liver of Apolipoprotein E (ApoE) Knockout mice revealed that atherosclerotic progression induced by feeding mice with high cholesterol diet (HCD) causes a significant downregulation of VTN mRNA as well as protein after 60 days. Promoter assay confirmed that cholesterol modulates the expression of VTN by influencing its promoter. Mimicking VTN reduction with siRNA in HCD fed ApoE Knockout mice, accelerated athero‐inflammation with an increase in NF‐kB, ICAM‐1, and VCAM‐1 at the site of the plaque along with upregulation of inflammatory proteins like MCP‐1 and IL‐1β in the plasma. Also, matrix metalloprotease (MMP)‐9 and MMP‐12 expression were increased and collagen content was decreased in the plaque, in VTN deficient condition. This might pose a challenge to plaque integrity. Human subjects with acute coronary syndrome or having risk factors of atherosclerosis have lower levels of VTN compared to healthy controls suggesting a clinical significance of plasma VTN in the pathophysiology of coronary artery disease. We establish that, VTN plays a pivotal role in cholesterol‐driven atherosclerosis and aortic inflammation and might be a useful indicator for atherosclerotic plaque burden and stability.
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spelling pubmed-88145622022-02-08 Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice Chakravarty, Devasmita Ray, Aleepta Guha Chander, Vivek Mabalirajan, Ulaganathan Mondal, Prakash Chandra Siddiqui, Khawer N. Sinha, Bishnu Prasad Konar, Aditya Bandyopadhyay, Arun FASEB Bioadv Research Articles Optimal cell spreading and interplay of vascular smooth muscle cells (VSMC), inflammatory cells, and cell adhesion molecules (CAM) are critical for progressive atherosclerosis and cardiovascular complications. The role of vitronectin (VTN), a major cell attachment glycoprotein, in the pathogenesis of atherosclerosis remains elusive. In this study, we attempt to examine the pathological role of VTN in arterial plaque progression and inflammation. We found that, relative expression analysis of VTN from the liver of Apolipoprotein E (ApoE) Knockout mice revealed that atherosclerotic progression induced by feeding mice with high cholesterol diet (HCD) causes a significant downregulation of VTN mRNA as well as protein after 60 days. Promoter assay confirmed that cholesterol modulates the expression of VTN by influencing its promoter. Mimicking VTN reduction with siRNA in HCD fed ApoE Knockout mice, accelerated athero‐inflammation with an increase in NF‐kB, ICAM‐1, and VCAM‐1 at the site of the plaque along with upregulation of inflammatory proteins like MCP‐1 and IL‐1β in the plasma. Also, matrix metalloprotease (MMP)‐9 and MMP‐12 expression were increased and collagen content was decreased in the plaque, in VTN deficient condition. This might pose a challenge to plaque integrity. Human subjects with acute coronary syndrome or having risk factors of atherosclerosis have lower levels of VTN compared to healthy controls suggesting a clinical significance of plasma VTN in the pathophysiology of coronary artery disease. We establish that, VTN plays a pivotal role in cholesterol‐driven atherosclerosis and aortic inflammation and might be a useful indicator for atherosclerotic plaque burden and stability. John Wiley and Sons Inc. 2021-11-19 /pmc/articles/PMC8814562/ /pubmed/35141476 http://dx.doi.org/10.1096/fba.2021-00108 Text en © 2021 The Authors. FASEB BioAdvances published by The Federation of American Societies for Experimental Biology. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Chakravarty, Devasmita
Ray, Aleepta Guha
Chander, Vivek
Mabalirajan, Ulaganathan
Mondal, Prakash Chandra
Siddiqui, Khawer N.
Sinha, Bishnu Prasad
Konar, Aditya
Bandyopadhyay, Arun
Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice
title Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice
title_full Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice
title_fullStr Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice
title_full_unstemmed Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice
title_short Systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice
title_sort systemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in apoe‐knockout mice
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814562/
https://www.ncbi.nlm.nih.gov/pubmed/35141476
http://dx.doi.org/10.1096/fba.2021-00108
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