Thioredoxin system activation is associated with the progression of experimental pulmonary arterial hypertension

Alexsandra Zimmer, Rayane Brinck Teixeira, Rosalia Lempk Constantin, Tânia Regina Gatelli Fernandes-Piedras, Cristina Campos-Carraro, Patrick Türck, Fernanda Visioli, Guilherme Baldo, Paulo Cavalheiro Schenkel, Alex Sander Araujo, Adriane Belló-Klein

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


In addition to being an antioxidant, thioredoxin (Trx) is known to stimulate signaling pathways involved in cell proliferation and to inhibit apoptosis. The aim of this study was to explore the role of Trx in some of these pathways along the progression of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male rats were first divided into two groups: monocrotaline (MCT - 60 mg/kg i.p.) and control (received saline), that were further divided into three groups: 1, 2, and 3 weeks. Animals were submitted to echocardiographic analysis. Right and left ventricles were used for the measurement of hypertrophy, through morphometric and histological analysis. The lung was prepared for biochemical and molecular analysis. One week after MCT injection, there was an increase in thioredoxin reductase (TrxR) activity, a reduction in glutathione reductase (GR) activity, and an increase in Trx-1 and vitamin D3 up-regulated protein-1 (VDUP-1) expression. Two weeks after MCT injection, there was an increase in VDUP-1, Akt and cleaved caspase-3 activation, and a decrease in Trx-1 and Nrf2 expression. PAH-induced by MCT promoted a reduction in Nrf2 and Trx-1 expression as well as an increase in Akt and VDUP-1 expression after three weeks. The increase in pulmonary vascular resistance was accompanied by increased TrxR activity, suggesting an association between the Trx system and functional changes in the progression of PAH. It seems that Trx-1 activation was an adaptive response to MCT administration to cope with pulmonary remodeling and disease progression, suggesting a potential new target for PAH therapeutics.

Original languageEnglish
Article number119917
JournalLife Sciences
StatePublished - 1 Nov 2021
Externally publishedYes


  • Cell signaling process
  • Experimental pulmonary arterial hypertension
  • Glutathione reductase
  • Thioredoxin
  • Time course
  • VDUP-1


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