Rotator Cuff Health, Pathology, and Repair in the Perspective of Hyperlipidemia

Rotator Cuff Injuries (RCI) are prevalent cause of shoulder pain affecting over 20% of the population in the USA. Surgical repair of the torn rotator cuff helps in relieving the pressure on the rotator cuff tendon and from symptoms, however tendon-to-bone healing after rotator cuff surgery still has a high failure rate. Hyperlipidemia has been strongly associated with RCI although the cellular and molecular mechanisms are largely unknown. The focus of this critical review is to further explore the role of hyperlipidemia in RCI and rotator cuff tissue repair to determine its implication as a risk factor for tears, repair, and retears. A literature review was conducted to elucidate the role of hyperlipidemia as an inflammatory mediator and catalyst for structural instability within the shoulder. The results from various studies were critically reviewed to summarize the relationship between hyperlipidemia and rotator cuff pathology. Hyperlipidemia induces LDL-particle entrapment within the dense regular collagen of rotator cuff tendons resulting in foam cell aggregation and macrophage recruitment. Subsequent inflammatory pathways including the JAK2/STAT3 pathway and NLRP3 inflammasome pathway led to persistent inflammation and Extracellular Matrix (ECM) degradation within the rotator cuff. While arthroscopic repair remains the most common treatment modality, nonsurgical treatment including statins, vitamin D, and targeting miRNA are also of therapeutic benefit. Hyperlipidemia interferes with arthroscopic repairs by inducing inflammation and stiffness within tendons and increases the risk of retears. Most notably, targeting underlying mechanisms influencing inflammation has large therapeutic value as a novel treatment strategy for the management of rotator cuff pathology.