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Locomotor and Diaphragm Muscle Mitochondrial Oxidative Capacity in Lung‐Targeted VEGF Gene Deleted Mice Exposed to Cigarette Smoke
Author(s) -
Witte Tyler,
Wong Fiona,
Lee Jasmine,
Fine Janelle,
Gutierrez Alma,
Bigby Timothy,
Can Daniel,
Breen Ellen
Publication year - 2016
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.30.1_supplement.742.9
Subject(s) - diaphragm (acoustics) , skeletal muscle , medicine , endocrinology , copd , lung , respiratory system , chemistry , physics , acoustics , loudspeaker
Locomotor skeletal muscle function is impaired in patients with chronic obstructive pulmonary disease (COPD). The mechanisms responsible for these skeletal muscle abnormalities are not well understood. We hypothesized that the severity of lung damage following chronic exposure to cigarette smoke (CS) would determine the mitochondrial oxidative capacity of locomotor and respiratory skeletal muscle. Adult VEGF LoxP mice with or without lung‐targeted VEGF gene deletion (5 months of age) were used as a model of progressively compromised static lung mechanics following exposure to 2 × 30 min of daily, nose‐only CS for an additional 4 months. Deletion of the VEGF gene was accomplished by instilling half the mice with AAV‐Cre one month before initiating CS exposure. The remaining mice received a control AAV (LacZ). Further, both groups (Cre and LacZ) were assigned either to CS exposure or room air control (RA). Mitochondrial respiration in permeabilized fiber bundles from the diaphragm and medial gastrocnemius was measured using high‐resolution respirometry. Gastrocnemius ADP‐stimulated O 2 consumption with malate and glutamate as substrates was 78±6%, 66±7% and 60±11% lower in CS‐LacZ, RA‐Cre, and CS‐Cre, respectively, than RA‐LacZ ( p <0.05). Gastrocnemius electron transport system capacity was 68±5% ( p <0.05), 53±11% ( p <0.05) and 48±21% (NS) lower in the CS‐LacZ, RA‐Cre, and CS‐Cre, respectively, than RA‐LacZ. Diaphragm ADP‐stimulated O −2 consumption was 56±9% lower in CS‐LacZ fibers than RA‐LacZ ( p <0.05). Diaphragm fiber electron transport system capacity was not different between the groups. Mice with a COPD‐like phenotype exhibited impaired locomotor muscle oxidative capacity irrespective of whether the lung damage was caused by cigarette smoke exposure or VEGF gene deletion. In contrast, diaphragm mitochondrial respiration only showed a deficit in ADP‐stimulated O 2 consumption with CS exposure. Thus, mitochondrial respiration in locomotor skeletal muscle appears to be less well‐preserved than diaphragm in this model of COPD. Support or Funding Information Department of Veterans Affairs