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β-Adrenergic Receptor Stimulation Maintains NCX-CaMKII Axis and Prevents Overactivation of IL6R-Signaling in

Ingrid Matzer1, Julia Voglhuber1,2, Mara Kiessling1

  • 1Department of Cardiology, Medical University of Graz, 8036 Graz, Austria.

Biomedicines
|July 27, 2022
PubMed

Insights

Excessive beta-adrenergic stimulation and tachycardia can harm the heart. This study reveals beta-adrenergic signaling protects against interleukin-6 receptor (IL6R) overactivation during increased workload, a finding crucial for heart disease therapies.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cellular Physiology

Background:

  • Excessive beta-adrenergic stimulation and tachycardia are known triggers of cardiac remodeling.
  • The precise cellular mechanisms underlying these effects on cardiomyocyte gene expression are not fully understood.

Purpose of the Study:

  • To investigate the impact of beta-adrenergic stimulation and tachycardia on cardiomyocyte gene expression profiles.
  • To elucidate the role of sodium-calcium exchanger (NCX) and calcium/calmodulin-dependent kinase II (CaMKII) in cardiac remodeling.
  • To explore the protective function of beta-adrenergic signaling in preventing cardiac pathology.

Main Methods:

  • Utilized neonatal rat ventricular cardiomyocytes and hypertensive Dahl salt-sensitive rats.
  • Assessed gene expression, including interleukin-6 receptor (IL6R).
  • Employed pharmacological interventions: isoprenaline, propranolol, and an NCX inhibitor (ORM-10962).

Main Results:

  • Tachycardia upregulated sodium-calcium exchanger (NCX) and activated nuclear calcium/calmodulin-dependent kinase II (CaMKII).
  • Isoprenaline ameliorated NCX upregulation and modulated CaMKII activity.
  • Tachycardia induced interleukin-6 receptor (IL6R) upregulation, which was prevented by isoprenaline but required simultaneous CaMKII activation and NCX inhibition.
  • Blunted beta-adrenergic signaling in hypertensive rats correlated with NCX upregulation and enhanced IL6R signaling.

Conclusions:

  • Beta-adrenergic signaling plays a protective role by preventing interleukin-6 receptor (IL6R) overactivation under increased cardiac workload.
  • This protective mechanism is compromised in cardiac pathologies.
  • Understanding these pathways can inform therapeutic strategies, particularly for patients on beta-blockers.
Keywords:
CaMKIIIL6Rcardiomyocytehypertensive cardiomyopathyhypertrophyisoprenalineβ-adrenergic signaling

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