Analysis of in vivo serpin functions in models of inflammatory vascular disease

Hao Chen, Sriram Ambadapadi, Erbin Dai, Liying Liu, Jordan R. Yaron, Liqiang Zhang, Alexandra Lucas

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Serpins have a wide range of functions in regulation of serine proteases in the thrombotic cascade and in immune responses, representing up to 2–10% of circulating proteins in the blood. Selected serpins also have cross-class inhibitory actions for cysteine proteases in inflammasome and apoptosis pathways. The arterial and venous systems transport blood throughout the mammalian body representing a central site for interactions between coagulation proteases and circulating blood cells (immune cells) and target tissues, a very extensive and complex interaction. While analysis of serpin functions in vitro in kinetics or gel shift assays or in tissue culture provides very necessary information on molecular mechanisms, the penultimate assessment of biological or physiological functions and efficacy for serpins as therapeutics requires study in vivo in whole animal models (some also consider cell culture to be an in vivo approach). Mouse models of arterial transplant with immune rejection as well as models of inflammatory vasculitis induced by infection have been used to study the interplay between the coagulation and immune response pathways. We describe here three in vivo vasculitis models that are used to study the roles of serpins in disease and as therapeutics. The models described include (1) mouse aortic allograft transplantation, (2) human temporal artery (TA) xenograft into immunodeficient mouse aorta, and (3) mouse herpes virus (MHV68)-induced inflammatory vasculitis in interferon-gamma receptor (IFNγR) knockout mice.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages157-182
Number of pages26
DOIs
StatePublished - 2018

Publication series

NameMethods in Molecular Biology
Volume1826
ISSN (Print)1064-3745

Keywords

  • Cysteine protease
  • Immune
  • Inflammation
  • Serine protease
  • Serpin
  • Thrombolysis
  • Thrombosis
  • Transplant
  • Vasculitis
  • Virus

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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