Plasma Protein Signatures of a Murine Venous Thrombosis Model and Slc44a2 Knockout Mice Using Quantitative-Targeted Proteomics
Venous thrombosis (VT) is a leading cause of mortality and morbidity in industrialized
countries. However, the precise mechanisms that trigger clotting in large veins are
not fully understood. Many genetic and acquired risk factors have been identified
for VT that alter blood flow, activate the endothelium, and alter the activity of
coagulation factors.[1] Many of these clotting factors are localized in the plasma, making analysis of this
blood compartment highly interesting for the understanding of VT.
As an alternative to activity- or antibody-based plasma protein assays, which provide
only limited information on single proteins in a sample, mass spectrometry (MS)-based
proteomics allows high-throughput, quantitative analysis of biomolecules. Indeed,
quantitative MS has been successfully applied to understand the pathomechanisms of
multiple diseases.[2]
In this issue of Thrombosis and Haemostasis, Tilburg et al attempt to uncover the plasma protein signatures upon induction of
VT using state-of-the-art MS-based targeted proteomics in combination with a murine
knockout model for SLC44A2, a recently identified susceptibility locus for VT.[3]
[4] With this elegant approach, they not only gain information about changes in the
plasma proteome in VT, but also demonstrate the great advantages of MS-based proteomics
such as specificity and the possibility to expand a limited sample volume to a huge
dataset.
The authors could show that the experimental induction of VT induced changes in plasma
levels of multiple proteins, including acute phase proteins as well as proteins related
to erythrocyte function. Strikingly, a strong sex-dependency of these changes was
observed that even overruled the effects of SLC44A2 deficiency.
By clarifying the plasma protein signatures in VT, the present study not only advances
our understanding of cardiovascular diseases but also introduces a new technique to
diagnose such pathologies, identify new targets for therapeutic interventions, and
quantify the effects of existing immunotherapeutics.
