Knockdown of coagulation factor VII has potential anticoagulant and anti-inflammatory effects in a mouse model of group A streptococcal sepsis

Juliane Köhler; Claudia Maletzki; Alexey S Revenko; Stefan Mikkat; Bernd Kreikemeyer; Sonja Oehmcke-Hecht

doi:10.1016/j.micinf.2023.105178

Knockdown of coagulation factor VII has potential anticoagulant and anti-inflammatory effects in a mouse model of group A streptococcal sepsis

Microbes Infect. 2023 Nov-Dec;25(8):105178. doi: 10.1016/j.micinf.2023.105178. Epub 2023 Jun 29.

Authors

Juliane Köhler¹, Claudia Maletzki², Alexey S Revenko³, Stefan Mikkat⁴, Bernd Kreikemeyer¹, Sonja Oehmcke-Hecht⁵

Affiliations

¹ Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Center, Rostock, Germany.
² Department of Medicine, Clinic III-Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany.
³ Department of Antisense Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA.
⁴ Core Facility Proteome Analysis; Rostock University Medical Center, Rostock, Germany.
⁵ Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Center, Rostock, Germany. Electronic address: [email protected].

PMID: 37392986
DOI: 10.1016/j.micinf.2023.105178

Abstract

Infections originating from subcutaneous tissues are among the most common invasive infections caused by group A streptococcus (GAS) and associated with systemic coagulation activation. The role of intrinsic coagulation factors on GAS virulence has recently been determined, but the role of the extrinsic coagulation factor VII is unknown. Using a mouse model, in which GAS-sepsis emerges from a subcutaneous infection, we show that FVII is a negative acute phase protein. F7 knockdown using antisense oligonucleotides resulted in an attenuated systemic coagulation activation and inflammatory response in septic animals. The findings indicate FVII's ability to modify the host response.

Keywords: Antisense oligonucleotides; FVII; Group A streptococcus; Sepsis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology
Anticoagulants / therapeutic use
Blood Coagulation
Factor VII* / pharmacology
Sepsis*

Substances

Factor VII
Anticoagulants
Anti-Inflammatory Agents