Overexpression of SOD2 in the diaphragm provides partial protection against ventilatorinduced diaphragm atrophy and contractile dysfunction.
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Mechanical ventilation (MV) is used clinically to maintain adequate pulmonary ventilation in patients that are unable to on their own. Unfortunately, an undesired sideeffect of prolonged MV is the rapid development of diaphragmatic atrophy and contractile dysfunction, termed collectively as ventilatorinduced diaphragm dysfunction (VIDD). The development of VIDD is clinically important because diaphragmatic weakness is a primary risk factor for difficult weaning from the ventilator. While the mechanism(s) leading to VIDD are not fully understood, increased mitochondrial production of reactive oxygen species (ROS) is a requirement for the development of VIDD. In this regard, superoxide dismutase 2 (SOD2) resides in the mitochondrial matrix and operates as the first line of defense to eliminate superoxide radicals. Therefore, we tested the hypothesis that overexpression of SOD2 in diaphragm fibers will protect against VIDD. Compared to control, viral transfection (rAAV9) of the SOD2 transgene in the diaphragm resulted in a ~70% increase in SOD2 protein abundance in diaphragm fibers. This overexpression of SOD2 in the diaphragm resulted in partial protection against VIDD by diminishing MVinduced diaphragmatic contractile dysfunction. Nonetheless, overexpression of SOD2 did not protect against MVinduced diaphragmatic atrophy. These findings demonstrate that increased expression of SOD2 alone in the diaphragm is not sufficient to prevent MVinduced diaphragm atrophy but does provide partial protection against MVinduced diaphragmatic contractile dysfunction.Support or Funding InformationSupported by NIH R01 AR064189 awarded to SKPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
