Survey of muscle characteristics after statin-induced rhabdomyolysis

Paul S. Phillips, M. Anthony Verity, Brian A. Schick, Giorgirene D. Vladutiu, Reijo Laaksonen, Matej Oresic, Raymond J. Hohl, Theodore P. Ciaraldi, Vikas P. Sukhatme, Stewart H. Lecker, Helene C.F. Cote, Henry Powell, William Davidson, Tanya Wolfson

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)

Abstract

Aims: The etiology of statin-induced rhabdomyolysis (SIR) remains obscure. Most explanations claim deficiency of one of the main end products of the HMG-CoA reductase pathway. Experimental work has rarely tested the skeletal muscle of humans after SIR. Methods: We compared muscle from ten SIR patients with muscle from eight age-matched, statin-naive control subjects. We evaluated differences in muscle histochemistry, sterol biochemistry, prenylated proteins, atrogin-1 and mitochondrial content to assess which characteristics distinguished the rhabdomyolysis reaction from normal age-matched muscle. Results: Plant sterols were significantly increased in muscle from SIR subjects compared with ontrol subjects. Ras was significantly reduced and there was a trend towards increased atrogin-1 in SIR subjects compared with ontrol subject muscle. There was no difference in cholesterol concentrations, mitochondrial content or coenzyme Q10 between groups. Conclusions: This evaluation of muscle from a small sample of patients with SIR demonstrates that differences in sitosterol:cholesterol ratio, the prenylated protein Ras and signals for muscle atrophy like atrogin-1, may distinguish this reaction from normal muscle.
Original languageEnglish
Pages (from-to)17-27
Number of pages11
JournalClinical Lipidology
Volume5
Issue number1
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Rhabdomyolysis
Muscles
coenzyme Q10
Cholesterol
Hydroxymethylglutaryl CoA Reductases
Phytosterols
ras Proteins
Muscular Atrophy
Surveys and Questionnaires
Sterols
Biochemistry
Skeletal Muscle

Keywords

  • coenzyme Q10
  • Ras
  • rhabdomyolysis
  • statin
  • toxicity

Cite this

Phillips, P. S., Verity, M. A., Schick, B. A., Vladutiu, G. D., Laaksonen, R., Oresic, M., ... Wolfson, T. (2010). Survey of muscle characteristics after statin-induced rhabdomyolysis. Clinical Lipidology, 5(1), 17-27. https://doi.org/10.2217/clp.09.83
Phillips, Paul S. ; Verity, M. Anthony ; Schick, Brian A. ; Vladutiu, Giorgirene D. ; Laaksonen, Reijo ; Oresic, Matej ; Hohl, Raymond J. ; Ciaraldi, Theodore P. ; Sukhatme, Vikas P. ; Lecker, Stewart H. ; Cote, Helene C.F. ; Powell, Henry ; Davidson, William ; Wolfson, Tanya. / Survey of muscle characteristics after statin-induced rhabdomyolysis. In: Clinical Lipidology. 2010 ; Vol. 5, No. 1. pp. 17-27.
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abstract = "Aims: The etiology of statin-induced rhabdomyolysis (SIR) remains obscure. Most explanations claim deficiency of one of the main end products of the HMG-CoA reductase pathway. Experimental work has rarely tested the skeletal muscle of humans after SIR. Methods: We compared muscle from ten SIR patients with muscle from eight age-matched, statin-naive control subjects. We evaluated differences in muscle histochemistry, sterol biochemistry, prenylated proteins, atrogin-1 and mitochondrial content to assess which characteristics distinguished the rhabdomyolysis reaction from normal age-matched muscle. Results: Plant sterols were significantly increased in muscle from SIR subjects compared with ontrol subjects. Ras was significantly reduced and there was a trend towards increased atrogin-1 in SIR subjects compared with ontrol subject muscle. There was no difference in cholesterol concentrations, mitochondrial content or coenzyme Q10 between groups. Conclusions: This evaluation of muscle from a small sample of patients with SIR demonstrates that differences in sitosterol:cholesterol ratio, the prenylated protein Ras and signals for muscle atrophy like atrogin-1, may distinguish this reaction from normal muscle.",
keywords = "coenzyme Q10, Ras, rhabdomyolysis, statin, toxicity",
author = "Phillips, {Paul S.} and Verity, {M. Anthony} and Schick, {Brian A.} and Vladutiu, {Giorgirene D.} and Reijo Laaksonen and Matej Oresic and Hohl, {Raymond J.} and Ciaraldi, {Theodore P.} and Sukhatme, {Vikas P.} and Lecker, {Stewart H.} and Cote, {Helene C.F.} and Henry Powell and William Davidson and Tanya Wolfson",
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Phillips, PS, Verity, MA, Schick, BA, Vladutiu, GD, Laaksonen, R, Oresic, M, Hohl, RJ, Ciaraldi, TP, Sukhatme, VP, Lecker, SH, Cote, HCF, Powell, H, Davidson, W & Wolfson, T 2010, 'Survey of muscle characteristics after statin-induced rhabdomyolysis', Clinical Lipidology, vol. 5, no. 1, pp. 17-27. https://doi.org/10.2217/clp.09.83

Survey of muscle characteristics after statin-induced rhabdomyolysis. / Phillips, Paul S.; Verity, M. Anthony; Schick, Brian A.; Vladutiu, Giorgirene D.; Laaksonen, Reijo; Oresic, Matej; Hohl, Raymond J.; Ciaraldi, Theodore P.; Sukhatme, Vikas P.; Lecker, Stewart H.; Cote, Helene C.F.; Powell, Henry; Davidson, William; Wolfson, Tanya.

In: Clinical Lipidology, Vol. 5, No. 1, 2010, p. 17-27.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Survey of muscle characteristics after statin-induced rhabdomyolysis

AU - Phillips, Paul S.

AU - Verity, M. Anthony

AU - Schick, Brian A.

AU - Vladutiu, Giorgirene D.

AU - Laaksonen, Reijo

AU - Oresic, Matej

AU - Hohl, Raymond J.

AU - Ciaraldi, Theodore P.

AU - Sukhatme, Vikas P.

AU - Lecker, Stewart H.

AU - Cote, Helene C.F.

AU - Powell, Henry

AU - Davidson, William

AU - Wolfson, Tanya

PY - 2010

Y1 - 2010

N2 - Aims: The etiology of statin-induced rhabdomyolysis (SIR) remains obscure. Most explanations claim deficiency of one of the main end products of the HMG-CoA reductase pathway. Experimental work has rarely tested the skeletal muscle of humans after SIR. Methods: We compared muscle from ten SIR patients with muscle from eight age-matched, statin-naive control subjects. We evaluated differences in muscle histochemistry, sterol biochemistry, prenylated proteins, atrogin-1 and mitochondrial content to assess which characteristics distinguished the rhabdomyolysis reaction from normal age-matched muscle. Results: Plant sterols were significantly increased in muscle from SIR subjects compared with ontrol subjects. Ras was significantly reduced and there was a trend towards increased atrogin-1 in SIR subjects compared with ontrol subject muscle. There was no difference in cholesterol concentrations, mitochondrial content or coenzyme Q10 between groups. Conclusions: This evaluation of muscle from a small sample of patients with SIR demonstrates that differences in sitosterol:cholesterol ratio, the prenylated protein Ras and signals for muscle atrophy like atrogin-1, may distinguish this reaction from normal muscle.

AB - Aims: The etiology of statin-induced rhabdomyolysis (SIR) remains obscure. Most explanations claim deficiency of one of the main end products of the HMG-CoA reductase pathway. Experimental work has rarely tested the skeletal muscle of humans after SIR. Methods: We compared muscle from ten SIR patients with muscle from eight age-matched, statin-naive control subjects. We evaluated differences in muscle histochemistry, sterol biochemistry, prenylated proteins, atrogin-1 and mitochondrial content to assess which characteristics distinguished the rhabdomyolysis reaction from normal age-matched muscle. Results: Plant sterols were significantly increased in muscle from SIR subjects compared with ontrol subjects. Ras was significantly reduced and there was a trend towards increased atrogin-1 in SIR subjects compared with ontrol subject muscle. There was no difference in cholesterol concentrations, mitochondrial content or coenzyme Q10 between groups. Conclusions: This evaluation of muscle from a small sample of patients with SIR demonstrates that differences in sitosterol:cholesterol ratio, the prenylated protein Ras and signals for muscle atrophy like atrogin-1, may distinguish this reaction from normal muscle.

KW - coenzyme Q10

KW - Ras

KW - rhabdomyolysis

KW - statin

KW - toxicity

U2 - 10.2217/clp.09.83

DO - 10.2217/clp.09.83

M3 - Article

VL - 5

SP - 17

EP - 27

JO - Clinical Lipidology

JF - Clinical Lipidology

SN - 1758-4299

IS - 1

ER -

Phillips PS, Verity MA, Schick BA, Vladutiu GD, Laaksonen R, Oresic M et al. Survey of muscle characteristics after statin-induced rhabdomyolysis. Clinical Lipidology. 2010;5(1):17-27. https://doi.org/10.2217/clp.09.83