The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction

Heba Salah, Meishan Li, Nicola Cacciani, Stefano Gastaldello, Hannah Ogilvie, Hazem Akkad, Arvind Venkat Namuduri, Valeria Morbidoni, Konstantin A. Artemenko, Gabor Balogh, Vicente Martinez-Redondo, Paulo Jannig, Yvette Hedström, Barry Dworkin, Jonas Bergquist, Jorge Ruas, Laszlo Vigh, Leonardo Salviati, Lars Larsson

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28 Citations (Scopus)


Ventilation-induced diaphragm dysfunction (VIDD) is a marked decline in diaphragm function in response to mechanical ventilation, which has negative consequences for individual patients' quality of life and for the health care system, but specific treatment strategies are still lacking. We used an experimental intensive care unit (ICU) model, allowing time-resolved studies of diaphragm structure and function in response to long-term mechanical ventilation and the effects of a pharmacological intervention (the chaperone co-inducer BGP-15). The marked loss of diaphragm muscle fiber function in response to mechanical ventilation was caused by posttranslational modifications (PTMs) of myosin. In a rat model, 10 days of BGP-15 treatment greatly improved diaphragm muscle fiber function (by about 100%), although it did not reverse diaphragm atrophy. The treatment also provided protection from myosin PTMs associated with HSP72 induction and PARP-1 inhibition, resulting in improvement of mitochondrial function and content. Thus, BGP-15 may offer an intervention strategy for reducing VIDD in mechanically ventilated ICU patients.

Original languageEnglish
Pages (from-to)350ra103
JournalScience Translational Medicine
Issue number350
Publication statusPublished - Aug 3 2016

ASJC Scopus subject areas

  • Medicine(all)

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    Salah, H., Li, M., Cacciani, N., Gastaldello, S., Ogilvie, H., Akkad, H., Venkat Namuduri, A., Morbidoni, V., Artemenko, K. A., Balogh, G., Martinez-Redondo, V., Jannig, P., Hedström, Y., Dworkin, B., Bergquist, J., Ruas, J., Vigh, L., Salviati, L., & Larsson, L. (2016). The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction. Science Translational Medicine, 8(350), 350ra103.