Protein Kinase C ß/Early Growth Response-1 Pathway
A Key Player in Ischemia, Atherosclerosis, and Restenosis
Shi-Fang Yan, MD*,
Evis Harja, MD,
Martin Andrassy, MD,
Tomoyuki Fujita, MD and
Ann Marie Schmidt, MD
Department of Surgery, Columbia University, New York, New York
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Figure 1 Protein kinase Cß-early growth response-1 (PKCß-Egr-1): implications for vascular stress. In this review, we provided the experimental evidence linking PKCß and Egr-1 to the pathogenesis of tissue injury. Studies support the premise that both acute stresses, such as that induced by hypoxia/hypoxemia and ischemia/reperfusion, as well as chronic stresses, such as that which occurs in atherosclerosis and restenosis, activate PKC, particularly the ß isoform. PKCß-mediated up-regulation of Egr-1 results in expression of cytokines, chemokines, procoagulant, and adhesion molecules; processes that lead to amplification of vascular inflammation, migration, and proliferation. Once set in motion, such processes, dependent on PKCß-Egr-1, lead to chronic vascular dysfunction and, ultimately, if left unchecked, tissue injury. Novel inhibitors of PKCß in clinical trials may hold promise for the treatment of these acute and chronic vascular diseases.
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