Simvastatin reduces fibrosis and protects against muscle weakness after massive rotator cuff tear

Abstract

Chronic rotator cuff tears are a common source of shoulder pain and disability, and patients with chronic cuff tears often have substantial weakness, fibrosis, inflammation, and fat accumulation. Identifying therapies to prevent the development of these pathologic processes will likely have a positive impact on clinical outcomes. Simvastatin is a drug with demonstrated anti-inflammatory and antifibrotic effects in many tissues but had not previously been studied in the context of rotator cuff tears. We hypothesized that after the induction of a massive supraspinatus tear, simvastatin would protect muscles from a loss of force production and fibrosis. We measured changes in muscle fiber contractility, histology, and biochemical markers of fibrosis and fatty infiltration in rats that received a full-thickness supraspinatus tear and were treated with either carrier alone or simvastatin. Compared with vehicle-treated controls, simvastatin did not have an appreciable effect on muscle fiber size, but treatment did increase muscle fiber specific force by 20%. Simvastatin also reduced collagen accumulation by 50% but did not affect triglyceride content of muscles. Several favorable changes in the expression of genes and other markers of inflammation, fibrosis, and regeneration were also observed. Simvastatin partially protected muscles from the weakness that occurs as a result of chronic rotator cuff tear. Fibrosis was also markedly reduced in simvastatin-treated animals. Whereas further studies are necessary, statin medication could potentially help improve outcomes for patients with rotator cuff tears.