Statins induce biochemical changes in the Achilles tendon after chronic treatment

Toxicology. 2013 Sep 15;311(3):162-8. doi: 10.1016/j.tox.2013.06.010. Epub 2013 Jul 4.


Statins have been widely prescribed as lipid-lowering drugs and are associated with tendon rupture. Therefore, this study aimed to evaluate the possible biochemical changes in the Achilles tendon of rats after chronic treatment with statins. Dosages of statins were calculated using allometric scaling with reference to the 80mg/day and 20mg/day, doses recommended for humans. The rats were divided into the following groups: treated with simvastatin (S-20 and S-80), treated with atorvastatin (A-20 and A-80), and the control group that received no treatment (C). Measurements of low-density lipoprotein (LDL) in the plasma were performed. The levels of non-collagenous proteins, glycosaminoglycans (GAGs) and hydroxyproline were quantified. Western blotting for collagen I was performed, and the presence of metalloproteinases (MMPs)-2 and -9 was investigated through zymography. The concentration of non-collagenous proteins in S-20 was less than the C group. There was a significant increase in pro-MMP-2 activity in A-80 group and in active MMP-2 in S-20 group compared to the C group. A significant increase in latent MMP-9 activity was observed in both the A-80 and S-20 groups when compared to C group. In the A-20 group, there was a lower amount of collagen I in relation to C group. In addition, a higher concentration of hydroxyproline was found in the S-20 group than the C group. The analysis of GAGs showed a significant increase in the A-20 group when compared to C group. The treatment induced remarkable alterations in the Achilles tendon and the response of the tissue seems to depend of the used statin dosage. The presence of MMP-2 and MMP-9 is evidence of the degradation and remodeling processes in the extracellular matrix of the tendons. Our results show that statins induce imbalance of extracellular matrix components and possibly induce microdamage in tendons.

Keywords: Atorvastatin; Collagen; Extracellular matrix; Simvastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / drug effects*
  • Achilles Tendon / metabolism
  • Animals
  • Cholesterol, LDL / blood
  • Collagen / metabolism
  • Glycosaminoglycans / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxyproline / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Rats
  • Rats, Wistar


  • Cholesterol, LDL
  • Glycosaminoglycans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Collagen
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • Hydroxyproline