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Delayed recovery of dysferlin‐null muscle from injurious lengthening contractions is likely due to increased macrophage infiltration
Author(s) -
Roche Joseph A,
Vanapalli Renuka,
Ru Lisa W,
Lovering Richard M,
Bloch Robert J
Publication year - 2009
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.23.1_supplement.600.1
Subject(s) - dysferlin , myogenesis , inflammation , medicine , skeletal muscle , myocyte , infiltration (hvac) , physics , thermodynamics
The mechanisms underlying dysferlinopathies are unknown. As dysferlin mediates sarcolemmal repair in vitro, we hypothesized that it is necessary for normal recovery from lengthening contractions in vivo. METHODS We studied the response to injury from 15 large‐strain lengthening contractions (LSI) or 150 small‐strain lengthening contractions (SSI) in the tibialis anterior muscle in dysferlin‐deficient, A/J (dysf‐) mice, and control, A/WySnJ (dysf+) mice. RESULTS Immediately after LSI and SSI, ~40% of torque was lost in both strains of mice. After LSI, dysf+ and dysf‐ muscles took 3 and 14 days, respectively, to recover completely; recovery in dysf‐ but not dysf+ was blunted by irradiation and accompanied by the loss of FDx‐labeled fibers 3‐14 days after injury, and significant myogenesis and inflammation. Recovery from SSI in dysf+ and dysf‐ muscles took 21 and 28 days, respectively; neither strain retained FDx 3 days after injury, and both showed significant myogenesis and inflammation, though inflammatory cell numbers were 5‐fold greater in dysf‐. Most infiltrating cells were CD68+ macrophages. Irradiation limited recovery to ~60% and ~50% of pre‐injury torque in dysf+ and dysf‐ muscles, respectively, but had no effect on inflammation. CONCLUSIONS Delayed recovery of dysf‐ muscle from lengthening contractions is associated with decreased myofiber survival and increased macrophage infiltration. This work was funded by the Jain Foundation.