Abstract
Arterial injury results in exposure of medial smooth muscle cells and adventitial fibroblasts to multiple growth factors that bind to specific cell surface receptors. These in turn activate second messengers and induce expression of immediate-early genes within minutes to hours after ligand binding to the receptor. Activation of the immediate-early genes results in passage of the stimulated cell from its nonproliferating, quiescent G0 state to the first phase of the cell cycle (G1). Coordination of the events that occur during the cell cycle is effected by a series of cyclin-dependent kinases and requires inactivation of several "tumor suppressor genes," including p53, p21, p16, p15, p27, and the retinoblastoma gene Rb, that inhibit the kinase activity of the cyclin/Cdk complexes. An understanding of the factors that regulate signal transduction, cell cycle progression, and programmed cell death has suggested several novel therapeutic strategies including (1) antisense oligonucleotide inhibition of proto-oncogene expression, (2) the use of molecular decoys or pharmacological therapies to block specific steps required for cell cycle progression, and (3) gene transfer of tumor suppressor genes. The apparent success of several of these strategies in animal models of restenosis suggests that these molecular therapies may play a valuable role in preventing intimal hyperplasia and restenosis after balloon angioplasty and vascular stenting.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.