Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis

Julio Madrigal-Matute, Carlos Ernesto Fernandez-Garcia, Luis Miguel Blanco-Colio, Elena Burillo, Ana Fortuño, Roxana Martinez-Pinna, Patricia Llamas-Granda, Oscar Beloqui, Jesus Egido, Guillermo Zalba, José Luis Martin-Ventura

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Abstract To assess the potential association between TRX-1/PRX-1 and NADPH oxidase (Nox) activity in vivo and in vitro, TRX-1/PRX-1 levels were assessed by ELISA in 84 asymptomatic subjects with known phagocytic NADPH oxidase activity and carotid intima-media thickness (IMT). We found a positive correlation between TRX-1/PRX-1 and NADPH oxidase-dependent superoxide production (r=0.48 and 0.47; p<0.001 for both) and IMT (r=0.31 and 0.36; p<0.01 for both) adjusted by age and sex. Moreover, asymptomatic subjects with plaques have higher PRX-1 and TRX plasma levels (p<0.01 for both). These data were confirmed in a second study in which patients with carotid atherosclerosis showed higher PRX-1 and TRX plasma levels than healthy subjects (p<0.001 for both). In human atherosclerotic plaques, the NADPH oxidase subunit p22phox colocalized with TRX-1/PRX-1 in macrophages (immunohistochemistry). In monocytes and macrophages, phorbol 12-myristate 13-acetate (PMA) induced NADPH activation and TRX-1/PRX-1 release to the extracellular medium, with a concomitant decrease in their intracellular levels, which was reversed by the NADPH inhibitor apocynin (Western blot). In loss-of-function experiments, genetic silencing of the NADPH oxidase subunit Nox2 blocked PMA-induced intracellular TRX-1/PRX-1 downregulation in macrophages. Furthermore, the PMA-induced release of TRX-1/PRX-1 involves the modulation of their redox status and exosome-like vesicles. TRX-1/PRX-1 levels are associated with NADPH oxidase-activity in vivo and in vitro. These data could suggest a coordinated antioxidant response to oxidative stress in atherothrombosis.

Original languageEnglish (US)
Article number12461
Pages (from-to)352-361
Number of pages10
JournalFree Radical Biology and Medicine
StatePublished - Jul 25 2015
Externally publishedYes


  • Atherosclerosis
  • Free radicals
  • NADPH oxidase
  • Oxidative stress
  • Peroxiredoxin
  • Thioredoxin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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