Cyclin-dependent protein kinases as therapeutic targets in cardiovascular disease

Excessive cell proliferation is thought to contribute to the development of neointimal lesions during the pathogenesis of atherosclerosis, restenosis and vessel bypass graft failure. Since cell cycle progression requires the sequential activation of cyclin-dependent kinases (CDKs), through their association with regulatory subunits dubbed cyclins, therapeutic strategies via CDK inhibition may reduce the burden of vascular proliferative disease. Some of these approaches may rely on the use of pharmacological CDK inhibitors that target the ATP-binding pocket of the catalytic site of CDK. Others are based on the overexpression of members of the family of CDK inhibitory proteins (CKIs), which associate with and inhibit the activity of CDK/cyclin holoenzymes. In this review, animal studies that document the efficacy of pharmacological agents and gene therapy approaches directly targeting CDK/cyclins for the treatment of vascular proliferative disease are discussed. Recent patent applications in this field are also analysed.