Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice.

Gupta, Ashok Kumar and Chopra, Bhupinder Singh and Vaid, Bhavna and Sagar, Amin and Raut, Sachin and Badmalia, Maulik D and Ashish, . and Khatri, Neeraj (2019) Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice. PloS one, 14 (4). ISSN 1932-6203

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Official URL: https://journals.plos.org/plosone/article?id=10.13...

Abstract

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.

Item Type: Article
Additional Information: Open Access
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 13 Aug 2019 12:50
Last Modified: 13 Aug 2019 12:50
URI: http://crdd.osdd.net/open/id/eprint/2349

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