Protein kinase Cα as a heart failure therapeutic target

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.”

Research Highlights
► Multiple papers have shown that PKCa regulates cardiac contractility.
► Deletion or genetic inhibition of PKCa increases cardiac function and protects from failure.
► Pharmacologic inhibition of PKCa protects from heart failure after injury.
► PKCa inhibitory drugs are promising therapeutics for human heart failure.