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

Abstract

Background 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 pathologies will likely have a positive impact on clinical outcomes. Simvastatin is a drug with demonstrated anti-inflammatory and anti-fibrotic effects in many tissues, but had not previously been studied in the context of rotator cuff tears. We hypothesized that following the induction of a massive supraspinatus tear, simvastatin would protect muscles from a loss of force production and fibrosis. Methods 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. Results Compared to 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 effect triglyceride content of muscles. Several favorable changes in the expression of genes and other markers of inflammation, fibrosis and regeneration were also observed. Conclusions 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. While further studies are necessary, statin medication could potentially help to improve outcomes for patients with rotator cuff tears.

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

“…We suspect that ECM gene expression levels for both VML and isolated DSM groups were elevated during earlier time points; an expression pattern that is consistent with muscle fibrosis. 43 Once a stable fibrotic scar was formed, the genes returned to the lower expression values we measured at 12 weeks. It is also important to note that the collagen I immunoreactivity and PCR analysis were conducted on samples taken from different tissue regions.…”

Investigating the cellular origin of rotator cuff muscle fatty infiltration and fibrosis after injury

“…It is postulated that increased fibrosis results in higher tension in the muscle in RC tears, thus making repair more challenging in chronic, retracted tears. In a clinical setting, fibrosis has been found in human RC tissue at time of repair and has been correlated with decreased force production and increased disruption of myofibril architecture 6,[22][23][24] . Fibrosis has also been identified as a direct cause of muscle dysfunction in muscular dystrophy.…”

“…Poor outcomes and high re-tear rates after surgery are thought to be due in part to these changes within the muscles 1 , and have been demonstrated to directly correlate with the amount of muscle atrophy and FI [2][3][4][5] . Although fibrosis is not well described in RC injuries, recent studies have linked poor muscle function to increased expression of fibrotic markers following RC injury 6,7 . Fibrosis is also found after other muscle injuries and has been shown to directly cause muscle dysfunction in muscular dystrophy.…”

Effects of Simvastatin on Alveolar Regeneration and Its Relationship to Exposure in Mice with Dexamethasone-Induced Emphysema

“…6) SV is one of the statins, which are widely used as medication for treating hypercholesterolemia and cardiovascular diseases. In addition, it was reported that the active form of SV, simvastatin hydroxy acid (SV-acid), 7) partially protected against muscle weakness after massive rotator cuff tear in rats, 8) affected the expression of heme oxygenase-1 in mice 9) and inhibited the induction of matrix metalloproteinase-9 in rats. 10) Moreover it had an antiinflammatory action and promoted epithelial cell proliferation.…”