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. 2020 Jul;52(6-7):1067-1069.
doi: 10.1007/s00726-020-02865-w. Epub 2020 Jun 27.

Creatine, guanidinoacetate and homoarginine in statin-induced myopathy

Axel Neu  1 , Sönke Hornig  1 , Ali Sasani  2 , Dirk Isbrandt  3   4 , Christian Gerloff  2 , Dimitris Tsikas  5 , Edzard Schwedhelm  6   7 , Chi-Un Choe  8
Affiliations

Creatine, guanidinoacetate and homoarginine in statin-induced myopathy

Axel Neu et al. Amino Acids. 2020 Jul.

Abstract

Our study evaluated the effect of creatine and homoarginine in AGAT- and GAMT-deficient mice after simvastatin exposure. Balestrino and Adriano suggest that guanidinoacetate might explain the difference between AGAT- and GAMT-deficient mice in simvastatin-induced myopathy. We agree with Balestrino and Adriano that our data shows that (1) creatine possesses a protective potential to ameliorate statin-induced myopathy in humans and mice and (2) homoarginine did not reveal a beneficial effect in statin-induced myopathy. Third, we agree that guanidinoacetate can be phosphorylated and partially compensate for phosphocreatine. In our study, simvastatin-induced damage showed a trend to be less pronounced in GAMT-deficient mice compared with wildtype mice. Therefore, (phospo) guanidinoacetate cannot completely explain the milder phenotype of GAMT-deficient mice, but we agree that it might contribute to ameliorate statin-induced myopathy in GAMT-deficient mice compared with AGAT-deficient mice. Finally, we agree with Balestino and Adriano that AGAT metabolites should further be evaluated as potential treatments in statin-induced myopathy.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

References

    1. Alfieri RR1, Bonelli MA, Cavazzoni A, Brigotti M, Fumarola C, Sestili P, Mozzoni P, De Palma G, Mutti A, Carnicelli D, Vacondio F, Silva C, Borghetti AF, Wheeler KP, Petronini PG. Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress. J Physiol. 2006;576(Pt 2):391–401. doi: 10.1113/jphysiol.2006.115006. - DOI - PMC - PubMed
    1. Balestrino M, Adriano E. Statin-induced myopathy prevented by creatine administration. BMJ Case Rep. 2018 doi: 10.1136/bcr-2018-225395. - DOI - PMC - PubMed
    1. Balestrino M, Adriano E. Presence of guanidinoacetate may compensate creatine absence and account for less statin-induced muscle damage in GAMT-deficient compared to AGAT-deficient mice. Amino Acids. 2020 doi: 10.1007/s00726-020-02838-z. - DOI - PubMed
    1. Choe CU, Atzler D, Wild PS, Carter AM, Böger RH, Ojeda F, Simova O, Stockebrand M, Lackner K, Nabuurs C, Marescau B, Streichert T, Müller C, Lüneburg N, De Deyn PP, Benndorf RA, Baldus S, Gerloff C, Blankenberg S, Heerschap A, Grant PJ, Magnus T, Zeller T, Isbrandt D, Schwedhelm E. Homoarginine levels are regulated by l-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies. Circulation. 2013;128(13):1451–1461. doi: 10.1161/CIRCULATIONAHA.112.000580. - DOI - PubMed
    1. Faller KME, Atzler D, McAndrew DJ, Zervou S, Whittington HJ, Simon JN, Aksentijevic D, Ten Hove M, Choe CU, Isbrandt D, Casadei B, Schneider JE, Neubauer S, Lygate CA. Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine. Cardiovasc Res. 2018;114(3):417–430. doi: 10.1093/cvr/cvx242. - DOI - PMC - PubMed

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