Le Hoangvi, Rai Vikrant, Agrawal Devendra K
Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California USA.
J Orthop Sports Med. 2024;6(3):198-213. doi: 10.26502/josm.511500161. Epub 2024 Sep 16.
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.
肩袖损伤是现役和正在训练的宇航员中最常见的损伤。根据美国疾病控制与预防中心（CDC）的数据，美国四分之一的成年人患有肩袖损伤，尤其影响冈上肌。高胆固醇血症是一种以低密度脂蛋白胆固醇水平升高为特征的疾病，在美国约五分之二的成年人中普遍存在，并且是肩部炎症和肩袖损伤修复后预后恶化的一个风险因素。慢性炎症是一种长期的低度炎症状态，可由高胆固醇血症等疾病引起，并导致肌肉萎缩。骨骼肌萎缩可由废用、衰老、营养不良和微重力等因素引起，目前缺乏经批准的药物治疗方法。因此，全面了解高胆固醇血症、慢性炎症和骨骼肌萎缩之间的关联对于制定有效的治疗策略至关重要。我们在尤卡坦小型猪身上进行了一项动物研究，以调查高胆固醇饮食对肩袖肌肉的影响。结果表明，高胆固醇血症猪的肩袖肌肉中存在慢性炎症，伴有促炎细胞因子和肌内脂肪细胞升高，以及骨骼肌萎缩。结果还显示，在高脂血症状态下，FOXO3/TRIM63/Titin轴上调。这些发现为通过靶向FOXO3/TRIM63/Titin轴制定更好的治疗策略以管理高胆固醇血症背景下的肩袖肌肉萎缩开辟了新的前景。
