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Protein Kinase A As a Promising Target for Heart Failure Drug Development

Overview
Journal Arch Med Res
Specialty General Medicine
Date 2019 Jan 16
PMID 30642654
Citations 20
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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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References
1.
Mathiyalagan P, Chang L, Du X, El-Osta A . Cardiac ventricular chambers are epigenetically distinguishable. Cell Cycle. 2010; 9(3):612-7. DOI: 10.4161/cc.9.3.10612. View

2.
Saad N, Elnakish M, Brundage E, Biesiadecki B, Kilic A, Ahmed A . Assessment of PKA and PKC inhibitors on force and kinetics of non-failing and failing human myocardium. Life Sci. 2018; 215:119-127. PMC: 6279240. DOI: 10.1016/j.lfs.2018.10.065. View

3.
Wang Z, Fermini B, Nattel S . Delayed rectifier outward current and repolarization in human atrial myocytes. Circ Res. 1993; 73(2):276-85. DOI: 10.1161/01.res.73.2.276. View

4.
Nishikimi T, Saito Y, Kitamura K, Ishimitsu T, Eto T, Kangawa K . Increased plasma levels of adrenomedullin in patients with heart failure. J Am Coll Cardiol. 1995; 26(6):1424-31. DOI: 10.1016/0735-1097(95)00338-X. View

5.
Shah A, Spurgeon H, Sollott S, Talo A, Lakatta E . 8-bromo-cGMP reduces the myofilament response to Ca2+ in intact cardiac myocytes. Circ Res. 1994; 74(5):970-8. DOI: 10.1161/01.res.74.5.970. View