S Zhazykbayeva, H Budde, M Kaçmaz, Y Zemedie, H Osman, R Hassoun, K Jaquet, I Akin, I El-Battrawy, M Herwig, N Hamdani
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Exploring PKG signaling as a therapeutic avenue for pressure overload, ischemia, and HFpEF.
Introduction: Heart failure (HF) is a complex and heterogeneous syndrome resulting from any diastolic or systolic dysfunction of the cardiac muscle. In addition to comorbid conditions, pressure overload, and myocardial ischemia are associated with cardiac remodeling which manifests as extracellular matrix (ECM) perturbations, impaired cellular responses, and subsequent ventricular dysfunction.
Areas covered: The current review discusses the main aspects of the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway (cGMP-PKG) pathway modulators and highlights the promising outcomes of its novel pharmacological boosters.
Expert opinion: Among several signaling pathways involved in the pathogenesis of pressure overload, ischemia and HF with preserved ejection fraction (HFpEF) is cGMP-PKG pathway. This pathway plays a pivotal role in the regulation of cardiac contractility, and modulation of cGMP-PKG signaling, contributing to the development of the diseases. Ventricular cardiomyocytes of HF patients and animal models are known to exhibit reduced cGMP levels and disturbed cGMP signaling including hypophosphorylation of PKG downstream targets. However, restoration of cGMP-PKG signaling improves cardiomyocyte function and promotes cardioprotective effects.
期刊介绍:
The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials.
The Editors welcome:
Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development.
Articles should not include clinical information including specific drugs and clinical trials.
Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs.
The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.