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Biochem Pharmacol. 2014 Mar 15;88(2):139-49. doi: 10.1016/j.bcp.2014.01.006. Epub 2014 Jan 16.

Protein kinase C isoforms in atherosclerosis: pro- or anti-inflammatory?

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Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Department of Comparative Medicine, Vascular Biology & Therapeutics Program, Yale University School of Medicine, 10 Amistad Street, Amistad Research Building 337c, CT 06520, USA.
Graduate Institute of Microbiology and Immunology, National Defense Medical Center, No.161, Section 6, Min-Chuan East Road, Taipei 114, Taiwan, ROC; Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan, R.OC. Electronic address:


Atherosclerosis is a pathologic condition caused by chronic inflammation in response to lipid deposition in the arterial wall. There are many known contributing factors such as long-term abnormal glucose levels, smoking, hypertension, and hyperlipidemia. Under the influence of such factors, immune and non-immune effectors cells are activated and participate during the progression of atherosclerosis. Protein kinase C (PKC) family isoforms are key players in the signal transduction pathways of cellular activation and have been associated with several aspects of the atherosclerotic vascular disease. This review article summarizes the current knowledge of PKC isoforms functions during atherogenesis, and addresses differential roles and disputable observations of PKC isoforms. Among PKC isoforms, both PKCβ and PKCδ are the most attractive and potential therapeutic targets. This commentary discusses in detail the outcomes and current status of clinical trials on PKCβ and PKCδ inhibitors in atherosclerosis-associated disorders like diabetes and myocardial infarction. The risk and benefit of these inhibitors for clinical purposes will be also discussed. This review summarizes what is already being done and what else needs to be done in further targeting PKC isoforms, especially PKCβ and PKCδ, for therapy of atherosclerosis and atherosclerosis-associated vasculopathies in the future.


Atherosclerosis; Endothelial cells; Macrophages; Protein kinase C; Vascular smooth muscle cells

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