Characterization of hsp27 kinases activated by elevated aortic pressure in heart

Benoit Boivin1, Maya Khairallah, Raymond Cartier

  • 1Montreal Heart Institute, 5000 Belanger St., Montreal, QC, H1T 1C8, Canada.

Insights

Elevated aortic pressure activates multiple small heat shock protein hsp27-kinases in rat hearts. These kinases, including MK2, MK3, and MK5, may play a role in hsp27

Area of Science:

  • Cardiovascular Physiology
  • Molecular Biology
  • Biochemistry

Background:

  • Chronic hemodynamic overload leads to cardiac remodeling, including left ventricular hypertrophy and fibrosis.
  • The small heat shock protein hsp27 is cardioprotective, requiring its phosphorylation for function.
  • Understanding hsp27 regulation under cardiac stress is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the activation of hsp27-kinase activities in response to elevated aortic pressure in isolated rat hearts.
  • To identify the specific kinases involved in phosphorylating hsp27 under pressure-induced stress.
  • To explore the potential of these kinases as targets for cardioprotective therapies.

Main Methods:

  • Isolated rat hearts were subjected to controlled retrograde perfusion at varying pressures.
  • Hsp27-kinase activity was measured in vitro by assessing hsp27 phosphorylation.
  • Immune complex assays, ion-exchange chromatography, and gel filtration were used to identify and characterize the involved kinases.

Main Results:

  • Elevated aortic pressure (60-120 mmHg) significantly increased overall hsp27-kinase activity.
  • Multiple kinase peaks (a, b, c) with distinct pressure-dependent activation profiles were identified.
  • Kinase peaks contained MK2, MK3, and MK5, with p38 MAPK and phospho-p38 MAPK present in peaks b and c.
  • At high pressure (120 mmHg), several distinct hsp27-kinase activities (p43, p49, p54, p66) were detected.

Conclusions:

  • Elevated aortic pressure activates multiple distinct hsp27-kinases in the heart.
  • These activated kinases, including MK2, MK3, and MK5, are implicated in the regulation of hsp27's cardioprotective effects.
  • Identifying these kinases offers potential therapeutic targets for cardioprotective interventions against cardiac stress.

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