In a recent article published in Circulation1, the team of Mustapha
Rouis2 at the Institute of Biology Paris-Seine has identified the
thioredoxin-80 (TRX-80) as a new marker for inflammatory and cardiovascular
diseases (CVD). The team showed that the concentration of this protein in the
blood increased with age. Of note, TRX-80 exerts pro-oxidant and
pro-inflammatory effects and enhances atherosclerosis. Researchers have
uncovered the molecular mechanisms that lead to the increase of this protein. Hence,
the plasma level of TRX-80 could be used as a marker to evaluate the risk of age-related
The thioredoxin system, including thioredoxin-1 (TRX-1)
and its cleaved form, TRX-80, is an essential system to maintain the oxidative
balance in the body. TRX-1, a 12 kDa ubiquitous protein, plays an anti-inflammatory,
anti-oxidant and anti-apoptotic role. In this study, researchers showed that the
plasma level of TRX-1 decreased with age, due to an enzymatic cleavage that
transforms this protein into a truncated form, TRX-80. In contrast to TRX-1, TRX-80
exerts pro-oxidant, pro-inflammatory, angiogenic and carcinogenic effects. TRX-80
also activates the inflammasome NLRP3, leading to the maturation of two pro-inflammatory
and pro-athérogenic cytokines, IL-1b and
IL-18. In addition, TRX-80 oriented macrophages to a pro-inflammatory M1-phenotype
which accumulate within atheromatous plaques. This has been demonstrated on
transgenic mice specifically overexpressing TRX-80 in macrophages. This
accumulation of M1-macrophages in atheromatous plaques makes the later instable,
fostering cardiovascular accidents.
This study explains, at least in part, why CVD and
probably other inflammatory diseases such as diabetes, cancer, and arthritis increase
with age. This work identifies TRX-80 as a new diagnostic marker for
inflammatory and CVD.
Caption: TRX-1, a 12 kDa
protein, is located in the cytoplasm. It protects cells, directly or
indirectly, against oxidative damages, inflammation and apoptosis.
Nevertheless, the plasma levels of TRX-1 decrease with age, while the plasma
levels of TRX-80 increase. This is due to the increase of both expression and
activity of 2 alpha-secretases (ADAM-10 and ADAM-17). TRX-80, unlike its native
form, is pro-inflammatory, pro-atherogenic and pro-carcinogenic factor. The
mechanisms involved in the regulation of the expression of these two alpha
secretases are not yet fully understood.
1. Human Plasma Thioredoxin-80 Increases with Age and in apoE-/-
Mice Induces Inflammation, Angiogenesis and Atherosclerosis ; Couchie D. et al, Circulation, 2017, May
2. Team Integrative Cellular Ageing and Inflammation (UMR UPMC/CNRS
8256-IBPS, INSERM U1164).