Protein kinase Cα as a heart failure therapeutic target.

Department of Pediatrics, Division of Molecular Cardiovascular Biology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Journal of Molecular and Cellular Cardiology (Impact Factor: 5.22). 10/2010; 51(4):474-8. DOI: 10.1016/j.yjmcc.2010.10.004
Source: PubMed

ABSTRACT Heart failure afflicts ~5 million people and causes ~300,000 deaths a year in the United States alone. Heart failure is defined as a deficiency in the ability of the heart to pump sufficient blood in response to systemic demands, which results in fatigue, dyspnea, and/or edema. Identifying new therapeutic targets is a major focus of current research in the field. We and others have identified critical roles for protein kinase C (PKC) family members in programming aspects of heart failure pathogenesis. More specifically, mechanistic data have emerged over the past 6-7 years that directly implicate PKCα, a conventional PKC family member, as a nodal regulator of heart failure propensity. Indeed, deletion of the PKCα gene in mice, or its inhibition in rodents with drugs or a dominant negative mutant and/or inhibitory peptide, has shown dramatic protective effects that antagonize the development of heart failure. This review will weigh all the evidence implicating PKCα as a novel therapeutic target to consider for the treatment of heart failure. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."



Available from