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Exploring PKG signaling as a therapeutic avenue for pressure overload, ischemia, and HFpEF

S Zhazykbayeva1,2, H Budde1,2, M Kaçmaz1,2,3

  • 1Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany.

Expert Opinion on Therapeutic Targets
|September 27, 2024
PubMed

Insights

The cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway is crucial in heart failure (HF). Restoring this signaling pathway improves cardiac function and offers cardioprotective effects in HF patients.

Area of Science:

  • Cardiovascular Medicine
  • Molecular Biology
  • Pharmacology

Background:

  • Heart failure (HF) is a complex syndrome involving cardiac remodeling and ventricular dysfunction.
  • Pathological processes like pressure overload and ischemia contribute to HF development.
  • The cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway is implicated in HF pathogenesis.

Purpose of the Study:

  • To review the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway.
  • To discuss modulators of the cGMP-PKG pathway.
  • To highlight novel pharmacological approaches targeting the cGMP-PKG pathway for heart failure.

Main Methods:

  • Literature review of the cGMP-PKG pathway in cardiovascular disease.
  • Analysis of signaling mechanisms in heart failure with preserved ejection fraction (HFpEF).
  • Evaluation of pharmacological interventions targeting the cGMP-PKG pathway.

Main Results:

  • Reduced cGMP levels and disturbed cGMP signaling are observed in cardiomyocytes of HF patients and animal models.
  • Hypophosphorylation of PKG downstream targets is a characteristic of impaired cGMP signaling in HF.
  • Restoration of cGMP-PKG signaling demonstrates potential for improving cardiomyocyte function and providing cardioprotection.

Conclusions:

  • The cGMP-PKG pathway plays a critical role in regulating cardiac contractility and HF development.
  • Modulation of cGMP-PKG signaling presents a promising therapeutic strategy for HF.
  • Novel pharmacological boosters of the cGMP-PKG pathway offer potential for improved treatment outcomes in heart failure.
Abstract

Keywords:
HFpEFPKGPressure overloadcGMPheart failureischemia

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