Thioredoxin 1 (TRX1) overexpression cancels the slow force response (SFR) development

ZAVALA, MAITE R.; DIAZ, ROMINA G; VILLA-ABRILLE, MARÍA C.; PEREZ, NESTOR G.

Frontiers in Cardiovascular Medicine

Frontiers Media SA

Lugar: Lausanne; Año: 2021

The stretch of cardiac muscle increases developed force in two phases. The first phase occursimmediately after stretch and is the expression of the Frank-Starling mechanism, while thesecond one or slow force response (SFR) occurs gradually and is due to an increase in thecalcium transient amplitude. An important step in the chain of events leading to the SFRgeneration is the increased production of reactive oxygen species (ROS) leading to redoxsensitive ERK1/2, p90RSK and NHE1 phosphorylation/activation. Conversely, suppression ofROS production blunts the SFR. The purpose of this study was to explore whetheroverexpression of the ubiquitously expressed antioxidant molecule TRX1 affects the SFRdevelopment and NHE1 phosphorylation. We did not detect any change in basal phophoERK1/2, phopho-p90RSK and NHE1 expression in mice with TRX1 overexpression comparedto wild-type (WT). Isolated papillary muscles from WT or TRX1 overexpressing mice werestretched from 92 to 98 % of its maximal length. A prominent SFR was observed in WT micethat was completely cancelled in TRX1 animals. Interestingly, myocardial stretch induced asignificant increase in NHE1 phosphorylation in WT mice that was not detected in TRX1overexpressing mice. These novel results suggest that magnification of cardiac antioxidantdefense power by overexpression of TRX1 precludes NHE1 phosphorylation/activation afterstretch, consequently blunting the SFR development.