Inflammation and Fatty Infiltration Correlates with Rotator Cuff Muscle Atrophy in Hypercholesterolemic Yucatan Microswine

Author(s): Hoangvi Le, Vikrant Rai, Devendra K. Agrawal

Rotator cuff injuries are the most common injuries among active and training astronauts. According to the CDC, 1 in 4 adults in the U.S. experience rotator cuff injuries, particularly affecting the supraspinatus muscle. Hypercholesterolemia, a condition characterized by high levels of LDL cholesterol, is prevalent in approximately 2 in 5 adults in the US and is a risk factor for worsened outcomes in shoulder inflammation and rotator cuff injury repairs. Chronic inflammation, a prolonged low-grade inflammatory state, can arise from conditions like hypercholesterolemia and contribute to muscle atrophy. Skeletal muscle atrophy can be caused by factors such as disuse, aging, malnutrition, and microgravity, and currently lacks approved drug therapies. Thus, gaining a comprehensive understanding of the associations between hypercholesterolemia, chronic inflammation, and skeletal muscle atrophy is imperative for developing effective strategies to manage this condition. We conducted an animal study in Yucatan miniswine to investigate the impact of a high-cholesterol diet on rotator cuff muscle. The results suggested the presence of chronic inflammation in rotator cuff muscle hypercholesterolemic swine, associated with elevated pro-inflammatory cytokines and intramuscular adipocytes, and skeletal muscle atrophy. The results also revealed upregulation of the FOXO3/TRIM63/Titin axis in a hyperlipidemic state. These findings open new perspectives for developing better treatment strategies by targeting the FOXO3/TRIM63/Titin axis to manage rotator cuff muscle atrophy in the context of hypercholesterolemia.