Diaphragm weakness and proteomics (global and redox) modifications in heart failure with reduced ejection fraction in rats

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of Florida
  • National University of Ireland, Galway

Details

Original languageEnglish (US)
Pages (from-to)238-249
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume139
StatusPublished - Feb 2020
Peer-reviewedYes

Abstract

Inspiratory dysfunction occurs in patients with heart failure with reduced ejection fraction (HFrEF) in a manner that depends on disease severity and by mechanisms that are not fully understood. In the current study, we tested whether HFrEF effects on diaphragm (inspiratory muscle) depend on disease severity and examined putative mechanisms for diaphragm abnormalities via global and redox proteomics. We allocated male rats into Sham, moderate (mHFrEF), or severe HFrEF (sHFrEF) induced by myocardial infarction and examined the diaphragm muscle. Both mHFrEF and sHFrEF caused atrophy in type IIa and IIb/x fibers. Maximal and twitch specific forces (N/cm2) were decreased by 19 ± 10% and 28 ± 13%, respectively, in sHFrEF (p < .05), but not in mHFrEF. Global proteomics revealed upregulation of sarcomeric proteins and downregulation of ribosomal and glucose metabolism proteins in sHFrEF. Redox proteomics showed that sHFrEF increased reversibly oxidized cysteine in cytoskeletal and thin filament proteins and methionine in skeletal muscle α-actin (range 0.5 to 3.3-fold; p < .05). In conclusion, fiber atrophy plus contractile dysfunction caused diaphragm weakness in HFrEF. Decreased ribosomal proteins and heighted reversible oxidation of protein thiols are candidate mechanisms for atrophy or anabolic resistance as well as loss of specific force in sHFrEF.

    Research areas

  • Cysteine, Methionine, Muscle atrophy, Muscle force, Oxidation

Citation formats

APA

Kelley, R. C., McDonagh, B., Brumback, B., Walter, G. A., Vohra, R., & Ferreira, L. F. (2020). Diaphragm weakness and proteomics (global and redox) modifications in heart failure with reduced ejection fraction in rats. Journal of Molecular and Cellular Cardiology, 139, 238-249. https://doi.org/10.1016/j.yjmcc.2020.02.002

Harvard

Kelley, RC, McDonagh, B, Brumback, B, Walter, GA, Vohra, R & Ferreira, LF 2020, 'Diaphragm weakness and proteomics (global and redox) modifications in heart failure with reduced ejection fraction in rats', Journal of Molecular and Cellular Cardiology, vol. 139, pp. 238-249. https://doi.org/10.1016/j.yjmcc.2020.02.002