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

Authors:
Ashok Kumar Gupta
Ashok Kumar Gupta
King George's Medical University
India
Bhupinder Singh Chopra
Bhupinder Singh Chopra
Council of Scientific and Industrial Research-Institute of Microbial Technology
Amin Sagar
Amin Sagar
CSIR-Institute of Microbial Technology
India
Sachin Raut
Sachin Raut
Indian Veterinary Research Institute
 Ashish
Ashish
Institute of Microbial Technology
India
Neeraj Khatri
Neeraj Khatri
From the Council of Scientific and Industrial Research-Institute of Microbial Technology
India

PLoS One 2019 19;14(4):e0215717. Epub 2019 Apr 19.

Division of Animal Facility, CSIR - Institute of Microbial Technology, Chandigarh, India.

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.

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Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215717PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474609PMC
April 2019

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