Histological Comparison of Arterial Thrombi in Mice and Men and the Influence of Cl-amidine on Thrombus Formation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Jan 3

PMID 29293656

Citations 37

Authors

Julia Novotny

Sue Chandraratne

Tobias Weinberger

Vanessa Philippi

Konstantin Stark

Andreas Ehrlich

Joachim Pircher

Ildiko Konrad

Paul Oberdieck

Anna Titova

Qendresa Hoti

Irene Schubert

Kyle R Legate

Nicole Urtz

Michael Lorenz

Jaroslav Pelisek

Steffen Massberg

Marie-Luise von Bruhl

Christian Schulz

Affiliations

Soon will be listed here.

Abstract

Aims: Medical treatment of arterial thrombosis is mainly directed against platelets and coagulation factors, and can lead to bleeding complications. Novel antithrombotic therapies targeting immune cells and neutrophil extracellular traps (NETs) are currently being investigated in animals. We addressed whether immune cell composition of arterial thrombi induced in mouse models of thrombosis resemble those of human patients with acute myocardial infarction (AMI).

Methods And Results: In a prospective cohort study of patients suffering from AMI, 81 human arterial thrombi were harvested during percutaneous coronary intervention and subjected to detailed histological analysis. In mice, arterial thrombi were induced using two distinct experimental models, ferric chloride (FeCl3) and wire injury of the carotid artery. We found that murine arterial thrombi induced by FeCl3 were highly concordant with human coronary thrombi regarding their immune cell composition, with neutrophils being the most abundant cell type, as well as the presence of NETs and coagulation factors. Pharmacological treatment of mice with the protein arginine deiminase (PAD)-inhibitor Cl-amidine abrogated NET formation, reduced arterial thrombosis and limited injury in a model of myocardial infarction.

Conclusions: Neutrophils are a hallmark of arterial thrombi in patients suffering from acute myocardial infarction and in mouse models of arterial thrombosis. Inhibition of PAD could represent an interesting strategy for the treatment of arterial thrombosis to reduce neutrophil-associated tissue damage and improve functional outcome.

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