title: 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 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.
  
  
  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 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.
  
  
  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. Whereas further studies are necessary, statin medication could potentially help improve outcomes for patients with rotator cuff tears.
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Max E
authors.initials: ME
authors.lastname: Davis
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Korn
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Gumucio
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Harning
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Anjali L
authors.initials: AL
authors.lastname: Saripalli
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Asheesh
authors.initials: A
authors.lastname: Bedi
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. Electronic address: cmendias@umich.edu.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015415:Biomarkers; D023081:CCAAT-Binding Factor / Q000235:genetics; D002908:Chronic Disease; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000235:genetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018908:Muscle Weakness / Q000209:etiology / Q000517:prevention & control*; D018995:Myosin Heavy Chains; D047495:PPAR gamma / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000235:genetics; D017006:Rotator Cuff / Q000187:drug effects* / Q000473:pathology; D000070636:Rotator Cuff Injuries; D012421:Rupture / Q000150:complications; D020069:Shoulder Pain / Q000209:etiology; D019821:Simvastatin / Q000494:pharmacology*; D000097382:CD68 Molecule
chemical_list: D000101:Acetyl-CoA C-Acetyltransferase; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D023081:CCAAT-Binding Factor; D016326:Extracellular Matrix Proteins; D018995:Myosin Heavy Chains; D047495:PPAR gamma; D019821:Simvastatin; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C000599076:ACAT1 protein, rat
keywords: HMG-CoA reductase inhibitor; Rotator cuff; fatty degeneration; fibrosis; muscle atrophy; myosteatosis; statin