Protein kinase C in heart failure: a therapeutic target?
Heart failure (HF) afflicts about 5 million people and causes 300,000 deaths a year in the United States alone. An integral part of the pathogenesis of HF is cardiac remodelling, and the signalling events that regulate it are a subject of intense research. Cardiac remodelling is the sum of responses of the heart to causes of HF, such as ischaemia, myocardial infarction, volume and pressure overload, infection, inflammation, and mechanical injury. These responses, including cardiomyocyte hypertrophy, myocardial fibrosis, and inflammation, involve numerous cellular and structural changes and ultimately result in a progressive decline in cardiac performance. Pharmacological and genetic manipulation of cultured heart cells and animal models of HF and the analysis of cardiac samples from patients with HF are all used to identify the molecular and cellular mechanisms leading to the disease. Protein kinase C (PKC) isozymes, a family of serine-threonine protein kinase enzymes, were found to regulate a number of cardiac responses, including those associated with HF. In this review, we describe the PKC isozymes that play critical roles in specific aspects of cardiac remodelling and dysfunction in HF.
Palaniyandi
Suresh Selvaraj
SS
Department of Chemical and Systems Biology, Stanford University School of Medicine, CCSR, Rm 3145A, 269 Campus Drive, Stanford, CA 94305-5174, USA.
Sun
Lihan
L
Ferreira
Julio Cesar Batista
JC
Mochly-Rosen
Daria
D
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005355:Fibrosis / Q000473:pathology; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000473:pathology; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D051381:Rats
D007527:Isoenzymes; D011493:Protein Kinase C