Therapeutic Potential for Protein Kinase C Inhibitor in Vascular Restenosis

Vascular restenosis, an overreaction of biological response to injury, is initialized by thrombosis and inflammation. This response is characterized by increased smooth muscle cell migration and proliferation. Available pharmacological treatments include anticoagulants, antiplatelet agents, immunosuppressants, and antiproliferation agents. Protein kinase C (PKC), a large family of serine/threonine kinases, has been shown to participate in various pathological stages of restenosis. Consequently, PKC inhibitors are expected to exert a wide range of pharmacological activities therapeutically beneficial for restenosis. In this review, the roles of PKC isozymes in platelets, leukocytes, endothelial cells, and smooth muscle cells are discussed, with emphasis given to smooth muscle cells. We will describe cellular and animal studies assessing prevention of restenosis with PKC inhibitors, particularly targeting -alpha, -beta, -delta, and -zeta isozymes. The delivery strategy, efficacy, and safety of such PKC regulators will also be discussed.