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Mechanisms of skeletal muscle deformity in hyperhomocysteinemia (1102.24)
Author(s) -
Veeranki Sudhakar,
Givvimani Srikanth,
Sathnur Pushpakumar,
Metreveli Naira,
Tyagi Suresh
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.1102.24
Subject(s) - skeletal muscle , arteriogenesis , medicine , perfusion , ischemia , endocrinology , hyperhomocysteinemia , hindlimb , cardiology , anatomy , homocysteine
Hyperhomocysteinemia (HHcy) is associated with elderly frailty, skeletal muscle malfunction and injury, reduced vascular integrity and function and mortality. Although HHcy was implicated in impairment of vasculogenesis after hind limb ischemia in murine models, the underlying mechanisms are unclear. We hypothesize that HHcy compromises perfusion, collateral formation and vasculogenesis through diminishing post‐ischemic vasculogenic responses in the muscle fibers. To test this hypothesis, we created femoral artery ligation in wild type (WT) and CBS+/‐ mice (a model for HHcy) and assessed tissue perfusion, collateral formation and skeletal muscle function using Laser Doppler perfusion imaging, barium angiography and fatigue tests. In addition, we evaluated post‐ischemic levels of VEGF, and levels of its muscle specific regulators: HIF‐1α and PGC‐1α in the skeletal muscle fibers. The observations indicated that dysregulation of VEGF, HIF‐1 alpha and PGC‐1 alpha levels in the CBS+/‐ mice ischemic skeletal muscles. Moreover, there was enhanced FOXO dependent atrogene transcription in the muscles and reduced muscle function after ischemia in the CBS+/‐ mice. These results suggest that HHcy adversely affects muscle specific ischemic responses and contribute to muscle frailty. Grant Funding Source : 1RO1HL108621