Protein kinase C and endothelial dysfunction in select vascular diseases

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Abstract
Protein kinases have crucial roles in intracellular signal transduction pathways that affect a wide range of biochemical processes, including apoptosis, metabolism, proliferation, and protein synthesis. Vascular endothelial cells are important regulators of vasomotor tone, tissue/organ perfusion, and inflammation. Since its discovery in the late 1970s, a growing body of literature implicates protein kinase C (PKC) in pathways involving angiogenesis, endothelial permeability, microvascular tone, and endothelial activation. Hence the objective of this review, to characterize the role of PKC in vascular endothelial cells. After discussing the basic principles of PKC structure and function, the focus shifts to abnormal PKC activity driving endothelial dysfunction in three major pathologies whose hallmark is significant vascular disease: diabetes mellitus, hypoxia/ischemia-reperfusion injury, and hypertension. Themes addressed include endothelial cell cycle derangement, endothelial oxidative stress, endothelial activation/inflammation, and impaired endothelial barrier integrity. Achieving a comprehensive understanding of endothelial cell-PKC pathophysiology may lead to development of new therapeutic targets for mitigating morbidity and mortality in these disease states.

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