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Overexpression of HSP72 protects against mechanical ventilation‐induced mitochondrial dysfunction and apoptotic signaling in the diaphragm (1091.1)
Author(s) -
Smuder Ashley,
Sollanek Kurt,
Min Kisuk,
Kwon Oh Sung,
Nelson W,
Powers Scott
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1091.1
Subject(s) - diaphragm (acoustics) , apoptosis , weakness , skeletal muscle , mechanical ventilation , medicine , cancer research , biology , microbiology and biotechnology , anatomy , biochemistry , physics , acoustics , loudspeaker
Mechanical ventilation (MV) is a life‐saving measure for patients in respiratory failure. However, prolonged MV results in diaphragm weakness, which contributes to problems in weaning from the ventilator. Therefore, developing effective countermeasures to protect against MV‐induced diaphragm weakness is important. In this regard, HSP72 overexpression has been demonstrated to protect against skeletal muscle dysfunction during a variety of conditions (i.e. hindlimb immobilization and cancer cachexia). Therefore, the current study tested the hypothesis that HSP72 overexpression in the diaphragm would protect against MV‐induced diaphragm dysfunction. Cause and effect was determined using a novel technique to overexpress HSP72 in the rat diaphragm via an adeno‐associated virus vector delivered directly to the diaphragm. Our results demonstrate that 12 hours of MV results in impaired mitochondrial function and a significant increase in mitochondrial ROS release, which leads to caspase‐3 activation and increased apoptosis within the diaphragm. Overexpression of HSP72 in the diaphragm protected against these alterations and inhibited MV‐induced apoptotic signaling. Therefore, HSP72 overexpression in the diaphragm may have therapeutic potential to combat MV‐induced diaphragm weakness. Grant Funding Source : This work was supported by NIH R01 AR064189 awarded to SK Powers.