The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

You'll have to ask your doctor what protocols are being used to prevent muscle atrophy. This will require lots more research that will never occur in humans before being useful. I could tell my calf muscle was atrophying because my AFO was getting looser. It wasn't even checked during any exam.

The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

Authors Márquez-Miranda V, Abrigo J, Rivera JC, Araya-Durán I, Aravena J, Simon F, Pacheco N, González-Nilo FD, Cabello-Verrugio C
Received 23 October 2016
Accepted for publication 1 February 2017
Published 13 March 2017 Volume 2017:12 Pages 1985—1999
DOI https://doi.org/10.2147/IJN.S125521
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Alexander Kharlamov
Peer reviewer comments 2
Editor who approved publication: Dr Thomas J. Webster

Valeria Márquez-Miranda,^1,2,* Johanna Abrigo,^3,4,* Juan Carlos Rivera,^3,4 Ingrid Araya-Durán,¹ Javier Aravena,^3,4 Felipe Simon,^3,4 Nicolás Pacheco,¹ Fernando Danilo González-Nilo,^1,2,5 Claudio Cabello-Verrugio<sup>3,4

1</sup>Center for Bioinformatics and Integrative Biology (CBIB), Facultad de Ciencias Biologicas, Universidad Andres Bello, Santiago, ²Fundación Fraunhofer Chile Research, Las Condes, ³Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas & Facultad de Medicina, Universidad Andres Bello, ⁴Millennium Institute on Immunology and Immunotherapy, Santiago, ⁵Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

^*These authors contributed equally to this work

Abstract: Angiotensin (1–7) (Ang-(1–7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1–7) carrier. Bioinformatics analysis showed that the Ang-(1–7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7)/PAMAM-OH complex, but not Ang-(1–7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1–7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1–7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1–7)/PAMAM-OH complex is an efficient delivery method for Ang-(1–7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

Keywords: muscle wasting, peptide delivery, carrier, anti-atrophic peptide

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