TY - JOUR
T1 - Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis
AU - Madrigal-Matute, Julio
AU - Fernandez-Garcia, Carlos Ernesto
AU - Blanco-Colio, Luis Miguel
AU - Burillo, Elena
AU - Fortuño, Ana
AU - Martinez-Pinna, Roxana
AU - Llamas-Granda, Patricia
AU - Beloqui, Oscar
AU - Egido, Jesus
AU - Zalba, Guillermo
AU - Martin-Ventura, José Luis
N1 - Funding Information:
We gratefully acknowledge the technical assistance of Idoya Rodríguez, Raquel Ros, and Ana Montoya. We particularly acknowledge the patients for their participation and the Biobank of the University of Navarra for its collaboration. This work was supported by the Spanish Ministerio de Ciencia y Tecnología ( SAF 2010-21852 , SAF 2010-20367 ), Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III , Redes RIC ( RD12/0042/00038 ) and Biobancos ( RD09/0076/00101 ), and Sociedad Española de Aterosclerosis . This project was also funded through an agreement between the Foundation for Applied Medical Research and UTE Project CIMA.
Publisher Copyright:
© 2015 Published by Elsevier Inc.
PY - 2015/7/25
Y1 - 2015/7/25
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Free radicals
KW - NADPH oxidase
KW - Oxidative stress
KW - Peroxiredoxin
KW - Thioredoxin
UR - http://www.scopus.com/inward/record.url?scp=84937896512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937896512&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2015.06.001
DO - 10.1016/j.freeradbiomed.2015.06.001
M3 - Article
C2 - 26117319
AN - SCOPUS:84937896512
SN - 0891-5849
VL - 86
SP - 352
EP - 361
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
M1 - 12461
ER -
