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Protein Kinase A as a Promising Target for Heart Failure Drug Development
Nancy S Saad1, Mohammad T Elnakish1, Amany A E Ahmed2
1Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
Insights
Protein kinase A (PKA) is crucial for heart function. This review explores PKA
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Heart failure (HF) is a widespread condition and a leading cause of hospitalization.
- HF incurs substantial economic costs globally, underscoring the need for effective prevention strategies.
- Protein kinase A (PKA) plays vital roles in cardiac contraction, metabolism, ion transport, and gene expression.
Purpose of the Study:
- To review the multifaceted roles of PKA and PKA-mediated signaling in both healthy hearts and the progression of HF.
- To highlight the impact of modulating cardiac PKA activity.
- To identify PKA as a potential therapeutic target for HF drug development.
Main Methods:
- Literature review focusing on PKA's function in cardiac physiology and pathophysiology.
- Analysis of PKA-mediated signal transduction pathways in the context of heart failure.
- Examination of studies investigating the effects of PKA inhibition and activation in cardiac models.
Main Results:
- PKA is integral to normal cardiac function, regulating key processes.
- Dysregulated PKA activity is implicated in the development of cardiomyopathy and heart failure.
- Modulating PKA activity presents a potential therapeutic avenue for HF.
Conclusions:
- PKA signaling is a critical determinant of cardiac health and disease.
- Targeting PKA offers a promising strategy for novel heart failure therapies.
- Further research into PKA modulation is warranted for effective HF treatment.
Abstract:
Heart failure (HF) is a clinical syndrome characterized by impaired ability of the heart to fill or eject blood. HF is rather prevalent and it represents the foremost reason of hospitalization in the United States. The costs linked to HF overrun those of all other causes of disabilities, and death in the United States and all over the developed as well as the developing countries which amplify the supreme significance of its prevention. Protein kinase (PK) A plays multiple roles in heart functions including, contraction, metabolism, ion fluxes, and gene transcription. Altered PKA activity is likely to cause the progression to cardiomyopathy and HF. Thus, this review is intended to focus on the roles of PKA and PKA-mediated signal transduction in the healthy heart as well as during the development of HF. Furthermore, the impact of cardiac PKA inhibition/activation will be highlighted to identify PKA as a potential target for the HF drug development.
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