title: PKC isozymes in chronic cardiac disease: possible therapeutic targets?
abstract: Cardiovascular disease is the leading cause of death in the United States. Therefore, identifying therapeutic targets is a major focus of current research. Protein kinase C (PKC), a family of serine/threonine kinases, has been identified as playing a role in many of the pathologies of heart disease. However, the lack of specific PKC regulators and the ubiquitous expression and normal physiological functions of the 11 PKC isozymes has made drug development a challenge. Here we discuss the validity of therapeutically targeting PKC, an intracellular signaling enzyme. We describe PKC structure, function, and distribution in the healthy and diseased heart, as well as the development of rationally designed isozyme-selective regulators of PKC functions. The review focuses on the roles of specific PKC isozymes in atherosclerosis, fibrosis, and cardiac hypertrophy, and examines principles of pharmacology as they pertain to regulators of signaling cascades associated with these diseases.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Churchill
authors.forename: Grant
authors.initials: G
authors.lastname: Budas
authors.forename: Alice
authors.initials: A
authors.lastname: Vallentin
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Koyanagi
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C