Diaphragm contractile weakness due to reduced mechanical loading: role of titin

Robbert J. van der Pijl, Hendrikus "Henk" Granzier, Coen A.C. Ottenheijm

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The diaphragm, the main muscle of inspiration, is constantly subjected to mechanical loading. Only during controlled mechanical ventilation, as occurs during thoracic surgery and in the intensive care unit, is mechanical loading of the diaphragm arrested. Animal studies indicate that the diaphragm is highly sensitive to unloading, causing rapid muscle fiber atrophy and contractile weakness; unloading-induced diaphragm atrophy and contractile weakness have been suggested to contribute to the difficulties in weaning patients from ventilator support. The molecular triggers that initiate the rapid unloading atrophy of the diaphragm are not well understood, although proteolytic pathways and oxidative signaling have been shown to be involved. Mechanical stress is known to play an important role in the maintenance of muscle mass. Within the muscle's sarcomere, titin is considered to play an important role in the stress-response machinery. Titin is a giant protein that acts as a mechanosensor regulating muscle protein expression in a sarcomere strain-dependent fashion. Thus titin is an attractive candidate for sensing the sudden mechanical arrest of the diaphragm when patients are mechanically ventilated, leading to changes in muscle protein expression. Here, we provide a novel perspective on how titin and its biomechanical sensing and signaling might be involved in the development of mechanical unloading-induced diaphragm weakness.

Original languageEnglish (US)
Pages (from-to)C167-C176
JournalAmerican journal of physiology. Cell physiology
Volume317
Issue number2
DOIs
StatePublished - Aug 1 2019

Fingerprint

Connectin
Diaphragm
Sarcomeres
Muscle Proteins
Muscles
Atrophy
Ventilator Weaning
Mechanical Stress
Muscular Atrophy
Artificial Respiration
Thoracic Surgery
Intensive Care Units
Maintenance

Keywords

  • diaphragm
  • loading
  • mechanical ventilation
  • titin

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Diaphragm contractile weakness due to reduced mechanical loading : role of titin. / van der Pijl, Robbert J.; Granzier, Hendrikus "Henk"; Ottenheijm, Coen A.C.

In: American journal of physiology. Cell physiology, Vol. 317, No. 2, 01.08.2019, p. C167-C176.

Research output: Contribution to journalArticle

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