HYPERCHOLESTROLEMIA INHIBITS GROWTH RELATED GENE EXPRESSION DURING ACUTE SKELETAL MUSCLE REGENERATION

Lemuel A. Brown, Richard A. Perry Jr., Jacob L. Brown, David E. Lee, Megan E. Rosa, Nicholas P. Greene & Tyrone A. Washington University of Arkansas, Fayetteville, Arkansas Roughly 30% of all Americans are diagnosed with high cholesterol, which is a risk factor for cardiovascular disease. Apolipoprotein E (ApoE) is a ligand for lipoprotein receptors that mediates the uptake of triglycerides, cholesterol, and other lipids into metabolic tissues and organs. Hence, the targeted disruption of the ApoE gene (ApoE-KO) creates a systemic environment high in cholesterol leading to numerous pathophysiological diseases. Skeletal muscle is a highly plastic tissue that has the capability to regenerate and repair after trauma occurs. The systemic environment influences the capacity of skeletal muscle regeneration. Yet, the effect of a high cholesterol environment on skeletal muscle regeneration has not been fully elucidated. PURPOSE: To determine if gene expression related to growth is impaired during skeletal muscle regeneration in ApoE-KO mice. METHODS: Age-matched female C57/BL6J (B6) mice and ApoE-KO mice (14-15 months old) were randomly administered either a damage-inducing myotoxin (Bupivacaine) into the tibialis anterior (TA, n = 4-8) or PBS (n= 6). Three days post-injection the TA was excised. Gene expression of growth and regeneration markers was determined by quantitative polymerase chain reaction. Data was analyzed by two-way ANOVA and post hoc LSD test. RESULTS: TA muscle wet weight in both B6 and ApoE-KO mice was reduced 9% and 14%, respectively (pIGF-1 gene expression in B6 mice (pMyoD gene expression increased 1.5 fold in mice (pCONCLUSION:After skeletal muscle damage occurs, markers of regeneration have been reported to increase. In a high cholesterol environment however, there was an inhibition of gene expression related to growth and regeneration that could negatively impact the recovery process. The ApoE knockout mice were provided by Rigel Pharmaceuticals