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Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice
The present study provides first evidence on the role of plasma gelsolin in protecting pulmonary thromboembolism and thrombosis in a mouse model. Gelsolin is the most abundant actin depolymerizing protein in plasma and its significantly depleted values have been reported in metabolic disorders inclu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474609/ https://www.ncbi.nlm.nih.gov/pubmed/31002695 http://dx.doi.org/10.1371/journal.pone.0215717 |
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author | Gupta, Ashok Kumar Chopra, Bhupinder Singh Vaid, Bhavna Sagar, Amin Raut, Sachin Badmalia, Maulik D. Ashish, Khatri, Neeraj |
author_facet | Gupta, Ashok Kumar Chopra, Bhupinder Singh Vaid, Bhavna Sagar, Amin Raut, Sachin Badmalia, Maulik D. Ashish, Khatri, Neeraj |
author_sort | Gupta, Ashok Kumar |
collection | PubMed |
description | The present study provides first evidence on the role of plasma gelsolin in protecting pulmonary thromboembolism and thrombosis in a mouse model. Gelsolin is the most abundant actin depolymerizing protein in plasma and its significantly depleted values have been reported in metabolic disorders including cardiovascular diseases and myocardial infarction. Though gelsolin replacement therapy (GRT) has been shown to be effective in some animal models, no such study has been reported for thrombotic diseases that are acutely in need of bio-therapeutics for immediate and lasting relief. Here, using mice model and recombinant human gelsolin (rhuGSN), we demonstrate the antithrombotic effect of gelsolin in ferric chloride induced thrombosis in carotid artery and thrombin induced acute pulmonary thromboembolism. In thrombosis model, arterial occlusion time was significantly enhanced upon subcutaneous (SC) treatment with 8 mg of gelsolin per mice viz. 15.83 minutes vs. 8 minutes in the placebo group. Pertinently, histopathological examination showed channel formation within the thrombi in the carotid artery following injection of gelsolin. Fluorescence molecular tomography imaging further confirmed that administration of gelsolin reduced thrombus formation following carotid artery injury. In thrombin-induced acute pulmonary thromboembolism, mice pretreated with aspirin or gelsolin showed 100 and 83.33% recovery, respectively. In contrast, complete mortality of mice was observed in vehicle treated group within 5 minutes of thrombin injection. Overall, our studies provide conclusive evidence on the thrombo-protective role of plasma gelsolin in mice model of pulmonary thromboembolism and thrombosis. |
format | Online Article Text |
id | pubmed-6474609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64746092019-05-03 Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice Gupta, Ashok Kumar Chopra, Bhupinder Singh Vaid, Bhavna Sagar, Amin Raut, Sachin Badmalia, Maulik D. Ashish, Khatri, Neeraj PLoS One Research Article The present study provides first evidence on the role of plasma gelsolin in protecting pulmonary thromboembolism and thrombosis in a mouse model. Gelsolin is the most abundant actin depolymerizing protein in plasma and its significantly depleted values have been reported in metabolic disorders including cardiovascular diseases and myocardial infarction. Though gelsolin replacement therapy (GRT) has been shown to be effective in some animal models, no such study has been reported for thrombotic diseases that are acutely in need of bio-therapeutics for immediate and lasting relief. Here, using mice model and recombinant human gelsolin (rhuGSN), we demonstrate the antithrombotic effect of gelsolin in ferric chloride induced thrombosis in carotid artery and thrombin induced acute pulmonary thromboembolism. In thrombosis model, arterial occlusion time was significantly enhanced upon subcutaneous (SC) treatment with 8 mg of gelsolin per mice viz. 15.83 minutes vs. 8 minutes in the placebo group. Pertinently, histopathological examination showed channel formation within the thrombi in the carotid artery following injection of gelsolin. Fluorescence molecular tomography imaging further confirmed that administration of gelsolin reduced thrombus formation following carotid artery injury. In thrombin-induced acute pulmonary thromboembolism, mice pretreated with aspirin or gelsolin showed 100 and 83.33% recovery, respectively. In contrast, complete mortality of mice was observed in vehicle treated group within 5 minutes of thrombin injection. Overall, our studies provide conclusive evidence on the thrombo-protective role of plasma gelsolin in mice model of pulmonary thromboembolism and thrombosis. Public Library of Science 2019-04-19 /pmc/articles/PMC6474609/ /pubmed/31002695 http://dx.doi.org/10.1371/journal.pone.0215717 Text en © 2019 Gupta et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gupta, Ashok Kumar Chopra, Bhupinder Singh Vaid, Bhavna Sagar, Amin Raut, Sachin Badmalia, Maulik D. Ashish, Khatri, Neeraj Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice |
title | Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice |
title_full | Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice |
title_fullStr | Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice |
title_full_unstemmed | Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice |
title_short | Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice |
title_sort | protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474609/ https://www.ncbi.nlm.nih.gov/pubmed/31002695 http://dx.doi.org/10.1371/journal.pone.0215717 |
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